المؤلفون: Elisabeth A. Murphy, Camila Guzman-Cardozo, Ashley C. Sukhu, Debby J. Parks, Malavika Prabhu, Iman Mohammed, Magdalena Jurkiewicz, Thomas J. Ketas, Sunidhi Singh, Marie Canis, Eva Bednarski, Alexis Hollingsworth, Embree M. Thompson, Dorothy Eng, Paul D. Bieniasz, Laura E. Riley, Theodora Hatziioannou, Yawei J. Yang

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-10 (2023)

مصطلحات موضوعية: Science

الوصف: Abstract The effects of heterogeneous infection, vaccination and boosting histories prior to and during pregnancy have not been extensively studied and are likely important for protection of neonates. We measure levels of spike binding antibodies in 4600 patients and their neonates with different vaccination statuses, with and without history of SARS-CoV-2 infection. We investigate neutralizing antibody activity against different SARS-CoV-2 variant pseudotypes in a subset of 259 patients and determined correlation between IgG levels and variant neutralizing activity. We further study the ability of maternal antibody and neutralizing measurements to predict neutralizing antibody activity in the umbilical cord blood of neonates. In this work, we show SARS-CoV-2 vaccination and boosting, especially in the setting of previous infection, leads to significant increases in antibody levels and neutralizing activity even against the recent omicron BA.1 and BA.5 variants in both pregnant patients and their neonates.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/6d381e7c295f4d94bdcb49c6735ccd37Test

المؤلفون: Savannah L. Herbek, Marie C. Smithgall, Elisabeth A. Murphy, Robert E. Schwartz, Shuibing Chen, Laura E. Riley, Heidi Stuhlmann, Yawei J. Yang, Ria Goswami

المصدر: Reproductive Medicine, Vol 3, Iss 4, Pp 303-319 (2022)

مصطلحات موضوعية: pregnancy, viral diseases, antivirals, maternal-fetal interface, placental ex vivo models, fetal ex vivo models, Reproduction, QH471-489

الوصف: Pregnancy is a period of elevated risk for viral disease severity, resulting in serious health consequences for both the mother and the fetus; yet antiviral drugs lack comprehensive safety and efficacy data for use among pregnant women. In fact, pregnant women are systematically excluded from therapeutic clinical trials to prevent potential fetal harm. Current FDA-recommended reproductive toxicity assessments are studied using small animals which often do not accurately predict the human toxicological profiles of drug candidates. Here, we review the potential of human maternal-fetal interface cellular models in reproductive toxicity assessment of antiviral drugs. We specifically focus on the 2- and 3-dimensional maternal placental models of different gestational stages and those of fetal embryogenesis and organ development. Screening of drug candidates in physiologically relevant human maternal-fetal cellular models will be beneficial to prioritize selection of safe antiviral therapeutics for clinical trials in pregnant women.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2673-3897/3/4/24Test; https://doaj.org/toc/2673-3897Test

الوصول الحر: https://doaj.org/article/6e7cb1bf898448a0ba232c52cf01aaa7Test

المؤلفون: Siyu Chen, Elisabeth A. Murphy, Angeline G. Pendergrass, Ashley C. Sukhu, Dorothy Eng, Magdalena Jurkiewicz, Iman Mohammed, Sophie Rand, Lisa J. White, Nathaniel Hupert, Yawei J. Yang

المصدر: Viruses, Vol 14, Iss 11, p 2408 (2022)

مصطلحات موضوعية: pregnant women, shielding during pregnancy, effectiveness, SARS-CoV-2, New York City, dynamic model, Microbiology, QR1-502

الوصف: Pregnant patients have increased morbidity and mortality in the setting of SARS-CoV-2 infection. The exposure of pregnant patients in New York City to SARS-CoV-2 is not well understood due to early lack of access to testing and the presence of asymptomatic COVID-19 infections. Before the availability of vaccinations, preventative (shielding) measures, including but not limited to wearing a mask and quarantining at home to limit contact, were recommended for pregnant patients. Using universal testing data from 2196 patients who gave birth from April through December 2020 from one institution in New York City, and in comparison, with infection data of the general population in New York City, we estimated the exposure and real-world effectiveness of shielding in pregnant patients. Our Bayesian model shows that patients already pregnant at the onset of the pandemic had a 50% decrease in exposure compared to those who became pregnant after the onset of the pandemic and to the general population.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1999-4915/14/11/2408Test; https://doaj.org/toc/1999-4915Test

الوصول الحر: https://doaj.org/article/b6d973392a2643dab54e47dbff4a2393Test

المؤلفون: Yuan Yuan, Shirley Xie, Jennifer C. Darnell, Andrew J. Darnell, Yuhki Saito, Hemali Phatnani, Elisabeth A. Murphy, Chaolin Zhang, Tom Maniatis, Robert B. Darnell

المصدر: Genome Biology, Vol 19, Iss 1, Pp 1-19 (2018)

مصطلحات موضوعية: Cell type-specific, CLIP, Motoneuron, NOVA, RNA, Alternative splicing, Biology (General), QH301-705.5, Genetics, QH426-470

الوصف: Abstract Background Alternative RNA processing plays an essential role in shaping cell identity and connectivity in the central nervous system. This is believed to involve differential regulation of RNA processing in various cell types. However, in vivo study of cell type-specific post-transcriptional regulation has been a challenge. Here, we describe a sensitive and stringent method combining genetics and CLIP (crosslinking and immunoprecipitation) to globally identify regulatory interactions between NOVA and RNA in the mouse spinal cord motoneurons. Results We developed a means of undertaking motoneuron-specific CLIP to explore motoneuron-specific protein–RNA interactions relative to studies of the whole spinal cord in mouse. This allowed us to pinpoint differential RNA regulation specific to motoneurons, revealing a major role for NOVA in regulating cytoskeleton interactions in motoneurons. In particular, NOVA specifically promotes the palmitoylated isoform of the cytoskeleton protein Septin 8 in motoneurons, which enhances dendritic arborization. Conclusions Our study demonstrates that cell type-specific RNA regulation is important for fine tuning motoneuron physiology and highlights the value of defining RNA processing regulation at single cell type resolution.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13059-018-1493-2Test; https://doaj.org/toc/1474-760XTest

الوصول الحر: https://doaj.org/article/cb685f73162747c5a46387f6f24edeabTest

المؤلفون: Marie C. Smithgall, Elisabeth A. Murphy, Nina Schatz-Siemers, Cathleen Matrai, Jiangling Tu, Rebecca N. Baergen, Yawei J. Yang

المصدر: American Journal of Obstetrics and Gynecology. 227:782-784

مصطلحات موضوعية: Obstetrics and Gynecology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8df3832a3e3be8edf7c82e202fe5f6a3Test
https://doi.org/10.1016/j.ajog.2022.06.039Test

المؤلفون: Yawei J. Yang, Elisabeth A. Murphy, Sunidhi Singh, Ashley C. Sukhu, Isabel Wolfe, Sanjana Adurty, Dorothy Eng, Jim Yee, Iman Mohammed, Zhen Zhao, Laura E. Riley, Malavika Prabhu

المصدر: Obstetrics & Gynecology. 139:373-380

مصطلحات موضوعية: Adult, COVID-19 Vaccines, Pregnancy, SARS-CoV-2, Immunoglobulin G, Immunization, Secondary, COVID-19, Humans, Obstetrics and Gynecology, Female, Antibodies, Viral, Fetal Blood, Retrospective Studies

الوصف: To describe maternal and umbilical cord blood anti-spike immunoglobulin (Ig)G levels at delivery with coronavirus disease 2019 (COVID-19) vaccination before and during pregnancy and to assess the association of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a vaccine booster dose with anti-spike maternal and umbilical cord IgG levels.We conducted a retrospective cohort study of women with self-reported COVID-19 vaccination (Pfizer-BioNTech, Moderna, or JohnsonJohnson/Janssen), including a booster dose, during or before pregnancy, who delivered at 34 weeks of gestation or more. Maternal and umbilical cord blood samples at delivery were analyzed for semi-quantitative anti-spike IgG. We examined the association between timing of maternal vaccination and maternal and umbilical cord anti-spike levels using a rank sum test. The relationships between a prior history of SARS-CoV-2 infection and maternal and umbilical cord anti-spike IgG levels, and between a booster dose and maternal and umbilical cord anti-spike levels, were also evaluated using a rank sum test.We included data from 1,359 vaccinated pregnant women, including 20 women who received a booster dose, and 1,362 umbilical cord samples. Maternal anti-spike IgG levels were detectable at delivery regardless of timing of vaccination throughout pregnancy among fully vaccinated women; however, early third-trimester vaccination was associated with the highest anti-spike IgG levels in maternal and umbilical cord blood. Among women with a history of SARS-CoV-2 infection, maternal and cord blood antibody response achieved with vaccination in early pregnancy was comparable with third-trimester vaccination in pregnant women without a history of SARS-CoV-2 infection. A booster dose in the third trimester was associated with maternal anti-spike IgG levels greater than third-trimester vaccination in women with or without a history of SARS-CoV-2 infection.Vaccination against COVID-19 before and throughout pregnancy was associated with detectable maternal anti-spike IgG levels at delivery. A complete vaccination course, prior history of SARS-CoV-2 infection, and a third-trimester booster dose were associated with the highest maternal and umbilical cord antibody levels.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::563517f1166b62011f0be29ba701eb33Test
https://doi.org/10.1097/aog.0000000000004693Test

المؤلفون: Yawei J. Yang, Malavika Prabhu, Elisabeth A. Murphy, Sunidhi Singh, Embree M. Thompson, Alexis Hollingsworth, Laura E. Riley

المصدر: American Journal of Obstetrics & Gynecology MFM. 5:100934

مصطلحات موضوعية: Obstetrics and Gynecology, General Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::a17a7d7a822b64e3091fd9141c2ec7e8Test
https://doi.org/10.1016/j.ajogmf.2023.100934Test

المؤلفون: Marie C, Smithgall, Elisabeth A, Murphy, Sophie, Rand, Ashley, Sukhu, Sunidhi, Singh, Nina, Schatz-Siemers, Cathleen, Matrai, Jiangling, Tu, Christine M, Salvatore, Malavika, Prabhu, Sallie, Permar, Laura E, Riley, Brian D, Robinson, Rebecca N, Baergen, Yawei J, Yang

المصدر: Journal of clinical and translational research. 8(5)

الوصف: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy has been on acute infections with limited data on the effect of distant infection.We examined placental pathology and neonatal outcomes in distant SARS-CoV-2 infection earlier in pregnancy compared to acute infections late in pregnancy/at birth and to non-SARS-CoV-2 infected patients with other placental pathologies/clinical presentations.Placentas birthed to unvaccinated patients with SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing and serology testing results from time of delivery were included in this study. A total of 514 singleton placentas between April 18, 2020, and July 26, 2021, were included: 77 acute SARS-CoV-2 infection (RT-PCR positive and serology negative); 222 distant SARS-CoV-2 infection (RT-PCR negative but serology IgG-positive); and 215 non-SARS-Cov-2 infected (RT-PCR negative, serology negative, and history negative) with other placental pathologies: preeclampsia/hypertension, intrauterine growth restriction (IUGR), diabetes, chorioamnionitis, and meconium. Placental pathology findings, Apgar scores, and neonatal birth weights were compared.Placentas from the acute group had significantly more villous agglutination (10.4%,Acute and distant SARS-CoV-2 infections present differing placental pathology.SARS-CoV-2 infection during pregnancy has demonstrable effects on the placenta with potential significant impacts for maternal and fetal health. Prevention of maternal SARS-CoV-2 infection, primarily through vaccination, remains the best mitigation strategy to prevent sequelae of maternal SARS-CoV-2 infection.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::79db055cdf88f466a07940cbdf4d4ca5Test
https://pubmed.ncbi.nlm.nih.gov/36518545Test

المؤلفون: Malavika Prabhu, Yawei J. Yang, Carrie D. Johnston, Elisabeth A. Murphy, Thomas J. Ketas, Randy Diaz-Tapia, Magdalena Jurkiewicz, Sabrina Racine-Brzostek, Iman Mohammed, Ashley C. Sukhu, Sunidhi Singh, Kimberly Forlenza, Sonali Iyer, Jim Yee, Dorothy Eng, Kristen Marks, Zhen Zhao, Per Johan Klasse, Sallie Permar, John P. Moore, Laura E. Riley

المصدر: American Journal of Obstetrics & Gynecology MFM. 5:100796

مصطلحات موضوعية: Obstetrics and Gynecology, General Medicine

الوصف: For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear.We sought to characterize the peak and longitudinal anti-S immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons.We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann-Whitney U test, and mixed analysis of variance test.Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immunoglobulin A, and immunoglobulin M responses were not associated with gestational age at vaccine initiation (all P.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post second dosage were significantly higher in nonpregnant persons (P.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P.001).The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6aa491d798b38906437937eb7f777bedTest
https://doi.org/10.1016/j.ajogmf.2022.100796Test

المؤلفون: Robert B. Darnell, Sarah K. Szwed, Elisabeth A Murphy, François Marchildon, Matt Kanke, Paul Cohen, Praveen Sethupathy, Sean O'Connor

المصدر: Genes Dev

مصطلحات موضوعية: Untranslated region, Adipose tissue, White adipose tissue, Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Adipocyte, microRNA, Adipocytes, Genetics, Animals, RNA, Messenger, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Binding Sites, Argonaute, Cell biology, Mice, Inbred C57BL, HITS-CLIP, MicroRNAs, MRNA Sequencing, Adipose Tissue, Gene Expression Regulation, chemistry, 030220 oncology & carcinogenesis, Argonaute Proteins, Chromatin Immunoprecipitation Sequencing, Resource/Methodology, Developmental Biology

الوصف: MicroRNAs (miRNAs) are short, noncoding RNAs that associate with Argonaute (AGO) to influence mRNA stability and translation, thereby regulating cellular determination and phenotype. While several individual miRNAs have been shown to control adipocyte function, including energy storage in white fat and energy dissipation in brown fat, a comprehensive analysis of miRNA activity in these tissues has not been performed. We used high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) to comprehensively characterize the network of high-confidence, in vivo mRNA:miRNA interactions across white and brown fat, revealing >20,000 unique AGO binding sites. When coupled with miRNA and mRNA sequencing, we found an inverse correlation between depot-enriched miRNAs and their targets. To illustrate the functionality of our HITS-CLIP data set in identifying specific miRNA:mRNA interactions, we show that miR-29 is a novel regulator of leptin, an adipocyte-derived hormone that coordinates food intake and energy homeostasis. Two independent miR-29 binding sites in the leptin 3′ UTR were validated using luciferase assays, and miR-29 gain and loss of function modulated leptin mRNA and protein secretion in primary adipocytes. This work represents the only experimentally generated miRNA targetome in adipose tissue and identifies multiple regulatory pathways that may specify the unique identities of white and brown fat.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dfb01540e5d21995e38261dbe48923bdTest
https://doi.org/10.1101/gad.345447.120Test