Roberto Romero

Bio: Roberto Romero is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Amniotic fluid & Chorioamnionitis. The author has an hindex of 151, co-authored 1516 publications receiving 108321 citations. Previous affiliations of Roberto Romero include University of Michigan & Weizmann Institute of Science.

Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study.

Abstract: Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, ERAP2 expression is altered in first trimester placentas of women destined to develop preeclampsia. A case-control design was used to test for associations between two SNPs in ERAP2, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal). We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (P = 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population. We report an association between fetal ERAP2 and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, ERAP2 has now been associated with preeclampsia in three populations. This provides strong evidence that ERAP2 plays a role in the development of preeclampsia.

Production of interleukin-6 by fetal and maternal cells in vivo during intraamniotic infection and in vitro after stimulation with interleukin-1.

Abstract: Amniotic fluid samples were obtained by transabdominal amniocentesis from 20 women in preterm labor (less than or equal to 34 wk gestation). Concentrations of IL-6 in culture-positive amniotic fluids (mean 8706 pg/mL, range 5100-14,446 pg/mL) were higher than those in culture-negative fluids (mean 1133 pg/mL, range 15-6534 pg/mL, p less than 0.0001) or fluids from healthy term pregnancies (mean 196 pg/mL, range less than or equal to 5-790 pg/mL, p less than 0.001). To assess possible sources of the Il-6 in amniotic fluid, we tested the ability of a variety of fetal and maternal cells to produce IL-6 in vitro after stimulation with IL-1, a cytokine known to stimulate IL-6 production. Very low concentrations of IL-6 were present in supernatants of cells not stimulated with IL-1; however, high concentrations were observed in supernatants of stimulated umbilical venous endothelial cells, decidual cells, and fetal and maternal blood mononuclear cells. To determine whether cells from adults produce IL-6 with kinetics similar to those of neonates, we incubated mononuclear cells obtained from blood of adults and term and preterm neonates with IL-1. After 6 h, IL-6 was detected in supernatants of adult cells and term neonatal cells, but not in supernatants of preterm cells. Concentrations at 18, 24, and 48 h were similar for adult and term cell supernatants, but were lower in supernatants of preterm cells. We also observed considerably more IL-6 mRNA accumulation in circulating mononuclear cells from adults than in those from neonates.

Prenatal diagnosis of sirenomelia.

Abstract: Prenatal sonographic findings of sirenomelia (or mermaid fetus) were retrospectively reviewed in eleven proven cases. Sonography showed oligohydramnios in all the cases, five (45%) of which had severe oligohydramnios that limited prenatal diagnosis by poor visibility. In five cases (45%), sirenomelia was correctly diagnosed by ultrasound; in the remainder, only bilateral renal agenesis was identified. All eleven fetuses had other associated malformations: congenital heart defects (4), skeletal deformities (10), and abdominal wall defects (4). Death resulted from termination of pregnancy in six cases and stillbirth in three cases. Two newborns died at 24 and 36 hours of neonatal life, respectively. We concluded that some cases of sirenomelia can be detected on prenatal sonograms by demonstration of a single lower extremity, oligohydramnios, and bilateral renal agenesis. Sirenomelia is a lethal condition and can be detectable in the second trimester of pregnancy, allowing for termination of pregnancy.

Maternal Serum Adiponectin Multimers In Gestational Diabetes

Abstract: Objective: Adiponectin, an adipokine with profound insulin-sensitizing effect, consists of heterogeneous species of multimers. These oligomeric complexes circulate as low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms and can exert differential biological effects. The aims of this study were to determine whether there is a change in circulating adiponectin multimers in the presence of gestational diabetes mellitus (GDM), overweight/obesity or with a treatment with sulfonylurea or insulin in patients with GDM. Study design: This cross-sectional study included women with: 1) normal pregnancy (n=149); and 2) patients with GDM (n=72). Thirty-three patients with GDM were managed with diet alone. Among the others 39 diabetic patients, 17 were treated with Glyburide and 22 with insulin. The study population was further stratified by first trimester body mass index (BMI) (normal weight <25 kg/m 2 vs. overweight/obese ≥25 kg/m 2 ). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Results: 1) The median maternal serum of total, HMW, MMW and LMW were lower in patients with GDM than in those with normal pregnancies (P < 0.001 for all comparisons) ; 2) patients with GDM had a lower HMW/total adiponectin ratio and a higher MMW/total and LMW/total adiponectin ratio than those with a normal pregnancy (P<0.001 for all comparisons); and 3) among GDM patients, there were no differences in the concentrations and relative distribution of adiponectin multimers between those who were managed with diet, and those who were treated with pharmacological agents. Conclusion: 1) GDM is characterized by a distinctive pattern of concentrations and relative distribution of adiponectin multimers akin to Type 2 diabetes mellitus; 2) dysregulation of adiponectin multimeres can provide a mechanistic basis for the association between adiposity and GDM.

limma powers differential expression analyses for RNA-sequencing and microarray studies

Abstract: limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets.

Abstract: Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein-protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein-protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.