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.

Function-Specific Intracellular Signaling Pathways Downstream of Heparin-Binding EGF-like Growth Factor Utilized by Human Trophoblasts

Abstract: Heparin-binding EGF-like growth factor (HBEGF) is expressed by trophoblast cells throughout gestation. First-trimester cytotrophoblast cells are protected from hypoxia-induced apoptosis because of the accumulation of HBEGF through a posttranscriptional autocrine mechanism. Exogenous application of HBEGF is cytoprotective in a hypoxia/reoxygenation (H/R) injury model and initiates trophoblast extravillous differentiation to an invasive phenotype. The downstream signaling pathways induced by HBEGF that mediate these various cellular activities were identified using two human first-trimester cytotrophoblast cell lines, HTR-8/SVneo and SW.71, with similar results. Recombinant HBEGF (1 nM) induced transient phosphorylation of MAPK3/1 (ERK), MAPK14 (p38), and AKT within 15 min and JNK after 1–2 h. To determine which downstream pathways regulate the various functions of HBEGF, cells were treated with specific inhibitors of the ERK upstream regulator MEK (U0126), the AKT upstream regulator phosphoinositide-3 (PI3)-kinase (LY294002), MAPK14 (SB203580), and JNK (SP600125), as well as with inactive structural analogues. Only SB203580 specifically prevented HBEGF-mediated rescue during H/R, while each inhibitor attenuated HBEGF-stimulated cell migration. Accumulation of HBEGF at reduced oxygen was blocked only by a combination of U0126, SB203580, and SP600125. We conclude that HBEGF advances trophoblast extravillous differentiation through coordinate activation of PI3 kinase, ERK, MAPK14, and JNK, while only MAPK14 is required for its antiapoptotic activity. Additionally, hypoxia induces an autocrine increase in HBEGF protein levels through MAPK14, JNK or ERK. These experiments reveal a complexity of the intracellular signaling circuitry that regulates trophoblast functions critical for implantation and placentation.

Biological implications of bi-directional fetomaternal cell traffic: a summary of a National Institute of Child Health and Human Development-sponsored conference

Abstract: Objective: The National Institute of Child Health and Human Development (NICHD) held a workshop on 27-28 July 2000 to bring together investigators working in the field of fetomaternal cellular and nucleic acid trafficking with the hope that this would stimulate further research into the biological implications of such phenomena. Methods: Invited speakers from all over the world presented their latest (unpublished) data. The conference proceedings were delayed until the present time to allow independent publication of the primary data. Results and conclusions: Bi-directional fetomaternal trafficking of cells and nucleic acids during pregnancy is now well established, through the use of molecular techniques including conventional and real-time polymerase chain reaction, as well as fluorescence in situ hybridization. In addition, human leukocyte antigen (HLA) is deposited in the skin of pregnant women. Feto-maternal trafficking is increased in some complications of pregnancy, such as pre-eclampsia, polyhydra...

Evidence supporting proteolytic cleavage of insulin-like growth factor binding protein-1 (IGFBP-1) protein in amniotic fluid.

Abstract: Objective: The purpose of this study was to determine if: 1) insulin-like growth factor binding protein-1 (IGFBP-1) in amniotic fluid (AF) exhibited proteolytic cleavage in cases of intra-amniotic inflammation; and 2) if the matrix metalloproteinases (MMP-3, MMP-8, MMP-9) in AF are associated with the degradation of IGFBP-1 in AF. Methods: AF samples (n=20) were obtained from preterm gestations with and without intra-amniotic inflammation. The form of IGFBP-1 in AF was assessed by Western blot analysis and AF MMP-8 concentration was measured by ELISA. Densitometric analysis of Western blot was performed and the fragmented/intact IGFBP-1 ratio was calculated. Proteolysis of AF IGFBP-1 by MMPs was evaluated by incubating AF with exogenous human MMP-3, MMP-8 or MMP-9, and by incubating recombinant human IGFBP-1 in AF with and without inflammation. Results: 1) IGFBP-1 was present in AF without inflammation as an intact form; however, the fragmented form was dominant in AF with inflammation; 2) the ratio of fragmented/intact IGFBP-1 was significantly higher in AF with inflammation than in AF without inflammation; 3) a higher ratio of fragmented/intact IGFBP-1 was associated with a higher concentration of MMP-8; 4) in-vitro proteolysis experiments showed that AF IGFBP-1 was degraded by exogenous human MMP-3, MMP-8 and MMP-9; 5) recombinant human IGFBP-1 was fragmented in AF with inflammation, but not in AF without inflammation. Conclusion: The fragmented form of AF IGFBP-1 was significantly increased in AF with intra-amniotic inflammation, and MMPs produced in AF with intra-amniotic inflammation were associated with the proteolytic change of AF IGFBP-1.

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.