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Yoel Sadovsky

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https://www.readbyqxmd.com/read/28923936/isolation-of-exosomes-from-whole-blood-by-integrating-acoustics-and-microfluidics
#1
Mengxi Wu, Yingshi Ouyang, Zeyu Wang, Rui Zhang, Po-Hsun Huang, Chuyi Chen, Hui Li, Peng Li, David Quinn, Ming Dao, Subra Suresh, Yoel Sadovsky, Tony Jun Huang
Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28879060/onset-of-human-preterm-and-term-birth-is-related-to-unique-inflammatory-transcriptome-profiles-at-the-maternal-fetal-interface
#2
Radek Bukowski, Yoel Sadovsky, Hani Goodarzi, Heping Zhang, Joseph R Biggio, Michael Varner, Samuel Parry, Feifei Xiao, Sean M Esplin, William Andrews, George R Saade, John V Ilekis, Uma M Reddy, Donald A Baldwin
BACKGROUND: Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples...
2017: PeerJ
https://www.readbyqxmd.com/read/28835115/-only-a-life-lived-for-others-is-worth-living-redox-signaling-by-oxygenated-phospholipids-in-cell-fate-decisions
#3
Yulia Y Tyurina, Indira Shrivastava, Vladimir A Tyurin, Gaowei Mao, Haider H Dar, Simon Watkins, Michael Epperly, Ivet Bahar, Anna A Shvedova, Bruce Pitt, Sally E Wenzel, Rama K Mallampalli, Yoel Sadovsky, Dmitry Gabrilovich, Joel S Greenberger, Hülya Bayır, Valerian E Kagan
SIGNIFICANCE: Oxygenated polyunsaturated lipids are known to play multi-functional roles as essential signals coordinating metabolism and physiology. Among them are well-studied eicosanoids and docosanoids that are generated via phospholipase A2 hydrolysis of membrane phospholipids and subsequent oxygenation of free polyunsaturated fatty acids (PUFA) by cyclooxygenases and lipoxygenases. Recent Advances: There is an emerging understanding that oxygenated PUFA-phospholipids also represent a rich signaling language with yet-to-be-deciphered details of the execution machinery-oxygenating enzymes, regulators, and receptors...
October 16, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28494237/microbial-vertical-transmission-during-human-pregnancy
#4
REVIEW
Nitin Arora, Yoel Sadovsky, Terence S Dermody, Carolyn B Coyne
Congenital infections with pathogens such as Zika virus, Toxoplasma gondii, Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster virus, Rubella, Cytomegalovirus, and Herpesviruses are a major cause of morbidity and mortality worldwide. Despite the devastating impact of microbial infections on the developing fetus, relatively little is known about how pathogens associated with congenital disease breach the placental barrier to transit vertically during human pregnancy. In this Review, we focus on transplacental transmission of pathogens during human gestation...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28487016/the-expression-level-of-c19mc-mirnas-in-early-pregnancy-and-in-response-to-viral-infection
#5
Tina M F Dumont, Jean-Francois Mouillet, Avaraham Bayer, Christina L Gardner, William B Klimstra, Dana G Wolf, Simcha Yagel, Fabiola Balmir, Anna Binstock, Joseph S Sanfilippo, Carolyn B Coyne, Jacob C Larkin, Yoel Sadovsky
INTRODUCTION: We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo. METHODS: We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR...
May 2017: Placenta
https://www.readbyqxmd.com/read/28396302/development-and-testing-of-the-myhealthypregnancy-app-a-behavioral-decision-research-based-tool-for-assessing-and-communicating-pregnancy-risk
#6
Tamar Krishnamurti, Alexander L Davis, Gabrielle Wong-Parodi, Baruch Fischhoff, Yoel Sadovsky, Hyagriv N Simhan
BACKGROUND: Despite significant advances in medical interventions and health care delivery, preterm births in the United States are on the rise. Existing research has identified important, seemingly simple precautions that could significantly reduce preterm birth risk. However, it has proven difficult to communicate even these simple recommendations to women in need of them. Our objective was to draw on methods from behavioral decision research to develop a personalized smartphone app-based medical communication tool to assess and communicate pregnancy risks related to preterm birth...
April 10, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/28289056/expression-and-trafficking-of-placental-micrornas-at-the-feto-maternal-interface
#7
Guojing Chang, Jean-François Mouillet, Takuya Mishima, Tianjiao Chu, Elena Sadovsky, Carolyn B Coyne, W Tony Parks, Urvashi Surti, Yoel Sadovsky
During pregnancy, placental trophoblasts at the feto-maternal interface produce a broad repertoire of microRNA (miRNA) species. These species include miRNA from the primate-specific chromosome 19 miRNA cluster (C19MC), which is expressed nearly exclusively in the placenta. Trafficking of these miRNAs among the maternal, placental, and fetal compartments is unknown. To determine miRNA expression and trafficking patterns during pregnancy, we sequenced miRNAs in triads of human placenta and of maternal and fetal blood and found large subject-to-subject variability, with C19MC exhibiting compartment-specific expression...
July 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28265065/formation-and-size-distribution-of-self-assembled-vesicles
#8
Changjin Huang, David Quinn, Yoel Sadovsky, Subra Suresh, K Jimmy Hsia
When detergents and phospholipid membranes are dispersed in aqueous solutions, they tend to self-assemble into vesicles of various shapes and sizes by virtue of their hydrophobic and hydrophilic segments. A clearer understanding of such vesiculation processes holds promise for better elucidation of human physiology and disease, and paves the way to improved diagnostics, drug development, and drug delivery. Here we present a detailed analysis of the energetics and thermodynamics of vesiculation by recourse to nonlinear elasticity, taking into account large deformation that may arise during the vesiculation process...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193876/vulnerability-of-primitive-human-placental-trophoblast-to-zika-virus
#9
Megan A Sheridan, Dinar Yunusov, Velmurugan Balaraman, Andrei P Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J Schust, Alexander W Franz, Yoel Sadovsky, Toshihiko Ezashi, R Michael Roberts
Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28108031/ifpa-meeting-2016-workshop-report-i-genomic-communication-bioinformatics-trophoblast-biology-and-transport-systems
#10
Christiane Albrecht, Julie C Baker, Cassidy Blundell, Shawn L Chavez, Lucia Carbone, Larry Chamley, Roberta L Hannibal, Nick Illsley, Peter Kurre, Louise C Laurent, Charles McKenzie, Diana Morales-Prieto, Priyadarshini Pantham, Alison Paquette, Katie Powell, Nathan Price, Balaji M Rao, Yoel Sadovsky, Carlos Salomon, Geetu Tuteja, Samantha Wilson, P F O'Tierney-Ginn
Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops covered innovative technologies applied to new and traditional areas of placental research: 1) genomic communication; 2) bioinformatics; 3) trophoblast biology and pathology; 4) placental transport systems.
January 11, 2017: Placenta
https://www.readbyqxmd.com/read/28099856/screening-bioactives-reveals-nanchangmycin-as-a-broad-spectrum-antiviral-active-against-zika-virus
#11
Keiko Rausch, Brent A Hackett, Nathan L Weinbren, Sophia M Reeder, Yoel Sadovsky, Christopher A Hunter, David C Schultz, Carolyn B Coyne, Sara Cherry
Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/27871470/the-function-of-mir-519d-in-cell-migration-invasion-and-proliferation-suggests-a-role-in-early-placentation
#12
REVIEW
Lan Xie, Yoel Sadovsky
The processes of proliferation, migration, and invasion of extravillous trophoblasts are critical for placental implantation and early development, and directly influence pregnancy outcome. Dysregulation of these processes has been associated with placental dysfunction, implicated in clinical conditions such as preeclampsia and placental accreta. Among diverse microRNA (miRNA) species that are expressed in placental trophoblasts, members of the chromosome 19 miRNA cluster (C19MC) stand out in their nearly exclusive expression in the placenta...
December 2016: Placenta
https://www.readbyqxmd.com/read/27780544/isolation-of-human-trophoblastic-extracellular-vesicles-and-characterization-of-their-cargo-and-antiviral-activity
#13
Yingshi Ouyang, Avraham Bayer, Tianjiao Chu, Vladimir A Tyurin, Valerian E Kagan, Adrian E Morelli, Carolyn B Coyne, Yoel Sadovsky
INTRODUCTION: Primary human trophoblasts release a repertoire of extracellular vesicles (EVs). Among them are nano-sized exosomes, which we found to suppress the replication of a wide range of diverse viruses. These exosomes contain trophoblastic microRNAs (miRNAs) that are expressed from the chromosome 19 miRNA cluster and exhibit antiviral properties. Here, we report our investigation of the cargo of placental EVs, focusing on the composition and the antiviral properties of exosomes, microvesicles, and apoptotic blebs...
November 2016: Placenta
https://www.readbyqxmd.com/read/27780532/intact-feto-placental-growth-in-microrna-210-deficient-mice
#14
Kamil Krawczynski, Takuya Mishima, Xin Huang, Yoel Sadovsky
MicroRNA-210 (miR-210) has been implicated in homeostatic adaptation during hypoxia. We hypothesized that miR-210 deficiency impacts feto-placental growth. As expected, mir-210 knockout (ko) mice exhibited markedly reduced placental miR-210 expression, compared to wild-type (wt) mice. Mating of mir-210 heterozygotes resulted in near Mendelian progeny distribution, with insignificant differences between wt and ko animals with regard to embryo or placental weight and gross morphology. Intriguingly, exposure of mice to non-severe hypoxia (O2 = 12%) between E11...
November 2016: Placenta
https://www.readbyqxmd.com/read/27627961/determinants-of-effective-lentivirus-driven-microrna-expression-in-vivo
#15
Takuya Mishima, Elena Sadovsky, Margaret E Gegick, Yoel Sadovsky
Manipulation of microRNA (miRNA) levels, including overexpression of mature species, has become an important biological tool, even motivating miRNA-based therapeutics. To assess key determinants of miRNA overexpression in a mammalian system in vivo, we sought to bypass the laborious generation of a transgenic animal by exploiting placental trophoblast-specific gene manipulation using lentiviral vectors, which has been instrumental in elucidating trophoblast biology. We examined the impact of several key components of miRNA stem loops and their flanking sequences on the efficiency of mature miRNA expression in vivo...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27066743/type-iii-interferons-produced-by-human-placental-trophoblasts-confer-protection-against-zika-virus-infection
#16
Avraham Bayer, Nicholas J Lennemann, Yingshi Ouyang, John C Bramley, Stefanie Morosky, Ernesto Torres De Azeved Marques, Sara Cherry, Yoel Sadovsky, Carolyn B Coyne
During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection...
May 11, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27051068/comparison-of-syncytiotrophoblast-generated-from-human-embryonic-stem-cells-and-from-term-placentas
#17
COMMENT
Shinichiro Yabe, Andrei P Alexenko, Mitsuyoshi Amita, Ying Yang, Danny J Schust, Yoel Sadovsky, Toshihiko Ezashi, R Michael Roberts
Human embryonic stem cells (ESCs) readily commit to the trophoblast lineage after exposure to bone morphogenetic protein-4 (BMP-4) and two small compounds, an activin A signaling inhibitor and a FGF2 signaling inhibitor (BMP4/A83-01/PD173074; BAP treatment). During differentiation, areas emerge within the colonies with the biochemical and morphological features of syncytiotrophoblast (STB). Relatively pure fractions of mononucleated cytotrophoblast (CTB) and larger syncytial sheets displaying the expected markers of STB can be obtained by differential filtration of dispersed colonies through nylon strainers...
May 10, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27016785/editorial-zika-virus-and-placenta
#18
EDITORIAL
Yoel Sadovsky, Vicki L Clifton, Martin Knöfler
No abstract text is available yet for this article.
April 2016: Placenta
https://www.readbyqxmd.com/read/26992671/isolation-of-basal-membrane-proteins-from-bewo-cells-and-their-expression-in-placentas-from-fetal-growth-restricted-pregnancies
#19
Soo-Young Oh, Jae Ryoung Hwang, Yoonna Lee, Suk-Joo Choi, Jung-Sun Kim, Jong-Hwa Kim, Yoel Sadovsky, Cheong-Rae Roh
INTRODUCTION: The syncytiotrophoblast, a key barrier between the mother and fetus, is a polarized epithelium composed of a microvillus and basal membrane (BM). We sought to characterize BM proteins of BeWo cells in relation to hypoxia and to investigate their expression in placentas from pregnancies complicated by fetal growth restriction (FGR). METHODS: We isolated the BM fraction of BeWo cells by the cationic colloidal silica method and identified proteins enriched in this fraction by mass spectrometry...
March 2016: Placenta
https://www.readbyqxmd.com/read/26973875/a-three-dimensional-culture-system-recapitulates-placental-syncytiotrophoblast-development-and-microbial-resistance
#20
Cameron A McConkey, Elizabeth Delorme-Axford, Cheryl A Nickerson, Kwang Sik Kim, Yoel Sadovsky, Jon P Boyle, Carolyn B Coyne
In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial role in fetal protection, many of the events that govern trophoblast fusion and protection from microbial infection are unknown. We describe a three-dimensional (3D)-based culture model using human JEG-3 trophoblast cells that develop syncytiotrophoblast phenotypes when cocultured with human microvascular endothelial cells...
March 2016: Science Advances
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