47 results on '"Slater, Damien"'
Search Results
2. Association between chlorine-treated drinking water, the gut microbiome, and enteric pathogen burden in young children in Haiti: An observational study
- Author
-
Chac, Denise, Slater, Damien M., Guillaume, Yodeline, Dunmire, Chelsea N., Ternier, Ralph, Vissières, Kenia, Juin, Stanley, Lucien, Mentor Ali Ber, Boncy, Jacques, Sanchez, Vanessa M., Dumayas, Mia G., Augustin, Gertrude Cene, Bhuiyan, Taufiqur R., Qadri, Firdausi, Chowdhury, Fahima, Khan, Ashraful I., Weil, Ana A., Ivers, Louise C., and Harris, Jason B.
- Published
- 2024
- Full Text
- View/download PDF
3. Effectiveness of the Euvichol® oral cholera vaccine at 2 years: A case-control and bias-indicator study in Haiti
- Author
-
Matias, Wilfredo R., Guillaume, Yodeline, Cene Augustin, Gertrude, Vissieres, Kenia, Ternier, Ralph, Slater, Damien M., Harris, Jason B., Franke, Molly F., and Ivers, Louise C.
- Published
- 2024
- Full Text
- View/download PDF
4. Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 IgG in Juba, South Sudan, 2020
- Author
-
Wiens, Kirsten E., Mawien, Pinyi Nyimol, Rumunu, John, Slater, Damien, Jones, Forrest K., Moheed, Serina, Caflisch, Andrea, Bior, Bior K., Jacob, Iboyi Amanya, Lako, Richard Lino, Guyo, Argata Guracha, Olu, Olushayo Oluseun, Maleghemi, Sylvester, Baguma, Andrew, Hassen, Juma John, Baya, Sheila K., Deng, Lul, Lessler, Justin, Demby, Maya N., Sanchez, Vanessa, Mills, Rachel, Fraser, Clare, Charles, Richelle C., Harris, Jason B., Azman, Andrew S., and Wamala, Joseph F.
- Subjects
Juba, South Sudan -- Health aspects ,Epidemics -- Statistics -- South Sudan ,Immunoglobulin G -- Statistics -- Health aspects ,Health - Abstract
Globally, >100 million cases and >2.6 million deaths had been attributed to coronavirus disease (COVID-19) as of March 14, 2021 (2). Most cases have been reported in Europe and the [...]
- Published
- 2021
- Full Text
- View/download PDF
5. Antibody responses after COVID-19 infection in patients who are mildly symptomatic or asymptomatic in Bangladesh
- Author
-
Shirin, Tahmina, Bhuiyan, Taufiqur Rahman, Charles, Richelle C., Amin, Shaheena, Bhuiyan, Imran, Kawser, Zannat, Rahat, Asifuzaman, Alam, Ahmed Nawsher, Sultana, Sharmin, Aleem, Md Abdul, Khan, Manjur Hossain, Khan, Samsad Rabbani, LaRocque, Regina C., Calderwood, Stephen B., Ryan, Edward T., Slater, Damien M., Banu, Sayera, Clemens, John, Harris, Jason B., Flora, Meerjady Sabrina, and Qadri, Firdausi
- Published
- 2020
- Full Text
- View/download PDF
6. Effectiveness of the Euvichol® oral cholera vaccine at 2 years: a case-control and bias-indicator study in Haiti
- Author
-
Matias, Wilfredo R., primary, Guillaume, Yodeline, additional, Augustin, Gertrude Cene, additional, Vissieres, Kenia, additional, Ternier, Ralph, additional, Slater, Damien M., additional, Harris, Jason B., additional, Franke, Molly F., additional, and Ivers, Louise C., additional
- Published
- 2023
- Full Text
- View/download PDF
7. Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection
- Author
-
Roach, David J, primary, Sridhar, Sushmita, additional, Oliver, Elizabeth, additional, Rao, Sowmya R, additional, Slater, Damien M, additional, Hwang, Wontae, additional, Hutt Vater, Kian, additional, Dinesh, Anupama, additional, Qadri, Firdausi, additional, Chisti, Mohammod J, additional, Pierce, Virginia M, additional, Turbett, Sarah E, additional, Bhattacharyya, Roby P, additional, Worby, Colin J, additional, Earl, Ashlee M, additional, LaRocque, Regina C, additional, and Harris, Jason B, additional
- Published
- 2023
- Full Text
- View/download PDF
8. Poor Sensitivity of Stool Culture Compared to Polymerase Chain Reaction in Surveillance for Vibrio cholerae in Haiti, 2018–2019
- Author
-
Guillaume, Yodeline, primary, Debela, Meti, additional, Slater, Damien, additional, Vissieres, Kenia, additional, Ternier, Ralph, additional, Franke, Molly F, additional, Harris, Jason B, additional, and Ivers, Louise C, additional
- Published
- 2023
- Full Text
- View/download PDF
9. Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection.
- Author
-
Roach, David J, Sridhar, Sushmita, Oliver, Elizabeth, Rao, Sowmya R, Slater, Damien M, Hwang, Wontae, Vater, Kian Hutt, Dinesh, Anupama, Qadri, Firdausi, Chisti, Mohammod J, Pierce, Virginia M, Turbett, Sarah E, Bhattacharyya, Roby P, Worby, Colin J, Earl, Ashlee M, LaRocque, Regina C, and Harris, Jason B
- Subjects
BACTEREMIA ,KLEBSIELLA ,SEQUENCE analysis ,CONFIDENCE intervals ,MANN Whitney U Test ,ACQUISITION of data ,KLEBSIELLA infections ,RISK assessment ,HOSPITAL mortality ,T-test (Statistics) ,GENOMES ,SYMPTOMS ,RESEARCH funding ,DESCRIPTIVE statistics ,CHI-squared test ,MEDICAL records ,DRUG resistance in microorganisms ,DATA analysis software ,ODDS ratio ,LOGISTIC regression analysis ,MICROBIAL virulence - Abstract
Background The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. Methods We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. Results Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2–12.8]; P <.001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2–12.4]; P <.001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. Conclusions These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. Disparities in SARS-CoV-2 Infection by Race, Ethnicity, Language, and Social Vulnerability: Evidence from a Citywide Seroprevalence Study in Massachusetts, USA
- Author
-
Matias, Wilfredo R., primary, Fulcher, Isabel R., additional, Sauer, Sara M., additional, Nolan, Cody P., additional, Guillaume, Yodeline, additional, Zhu, Jack, additional, Molano, Francisco J., additional, Uceta, Elizabeth, additional, Collins, Shannon, additional, Slater, Damien M., additional, Sánchez, Vanessa M., additional, Moheed, Serina, additional, Harris, Jason B., additional, Charles, Richelle C., additional, Paxton, Ryan M., additional, Gonsalves, Sean F., additional, Franke, Molly F., additional, and Ivers, Louise C., additional
- Published
- 2023
- Full Text
- View/download PDF
11. Reemergence of Cholera in Haiti
- Author
-
Rubin, Daniel H.F., primary, Zingl, Franz G., additional, Leitner, Deborah R., additional, Ternier, Ralph, additional, Compere, Valusnor, additional, Marseille, Samson, additional, Slater, Damien, additional, Harris, Jason B., additional, Chowdhury, Fahima, additional, Qadri, Firdausi, additional, Boncy, Jacques, additional, Ivers, Louise C., additional, and Waldor, Matthew K., additional
- Published
- 2022
- Full Text
- View/download PDF
12. Identifying Recent Cholera Infections Using a Multiplex Bead Serological Assay
- Author
-
Jones, Forrest K., primary, Bhuiyan, Taufiqur R., additional, Muise, Rachel E., additional, Khan, Ashraful I., additional, Slater, Damien M., additional, Hutt Vater, Kian Robert, additional, Chowdhury, Fahima, additional, Kelly, Meagan, additional, Xu, Peng, additional, Kováč, Pavol, additional, Biswas, Rajib, additional, Kamruzzaman, Mohammad, additional, Ryan, Edward T., additional, Calderwood, Stephen B., additional, LaRocque, Regina C., additional, Lessler, Justin, additional, Charles, Richelle C., additional, Leung, Daniel T., additional, Qadri, Firdausi, additional, Harris, Jason B., additional, and Azman, Andrew S., additional
- Published
- 2022
- Full Text
- View/download PDF
13. Reemergence of cholera in Haiti
- Author
-
Rubin, Daniel H. F., primary, Zingl, Franz G., additional, Leitner, Deborah R., additional, Ternier, Ralph, additional, Compere, Valusnor, additional, Marseille, Samson, additional, Slater, Damien, additional, Harris, Jason B., additional, Chowdhury, Fahima, additional, Qadri, Firdausi, additional, Boncy, Jacques, additional, Ivers, Louise C., additional, and Waldor, Matthew K., additional
- Published
- 2022
- Full Text
- View/download PDF
14. Identifying recent cholera infections using a multiplex bead serological assay
- Author
-
Jones, Forrest Kirby, primary, Bhuiyan, Md. Taufiqur Rahman, additional, Mills, Rachel, additional, Khan, Ashraful Islam K, additional, Slater, Damien, additional, Vater, Kian Robert Hutt, additional, Chowdhury, Fahima, additional, Kelly, Meagan, additional, Xu, Peng, additional, Kovac, Pavol, additional, Biswas, Rajib, additional, Kamruzzaman, Mohammad, additional, Ryan, Edward T, additional, Calderwood, Stephen B, additional, LaRocque, Regina C, additional, Lessler, Justin, additional, Charles, Richelle, additional, Leung, Daniel, additional, Qadri, Firdausi, additional, Harris, Jason B, additional, and Azman, Andrew S, additional
- Published
- 2022
- Full Text
- View/download PDF
15. 396. Disparities in SARS-CoV-2 Antibody Prevalence: Findings from a Citywide Serosurvey in Holyoke, Massachusetts, November 2020–January 2021
- Author
-
Matias, Wilfredo, primary, Fulcher, Isabel, additional, Nolan, Cody, additional, Guillaume, Yodeline, additional, Zhu, Jack, additional, Molano, Francisco, additional, Uceta, Elizabeth, additional, Collins, Shannon, additional, Slater, Damien, additional, Sanchez, Vanessa, additional, Moheed, Serina, additional, Harris, Jason, additional, Charles, Richelle, additional, Paxton, Ryan, additional, Gonsalves, Sean, additional, Franke, Molly, additional, and Ivers, Louise, additional
- Published
- 2021
- Full Text
- View/download PDF
16. Disparities in SARS-CoV-2 exposure: evidence from a citywide seroprevalence study in Holyoke, Massachusetts, USA
- Author
-
Matias, Wilfredo R., primary, Fulcher, Isabel R., additional, Sauer, Sara M., additional, Nolan, Cody P., additional, Guillaume, Yodeline, additional, Zhu, Jack, additional, Molano, Francisco J., additional, Uceta, Elizabeth, additional, Collins, Shannon, additional, Slater, Damien M., additional, Sánchez, Vanessa M., additional, Moheed, Serina, additional, Harris, Jason B., additional, Charles, Richelle C., additional, Paxton, Ryan M., additional, Gonsalves, Sean F., additional, Franke, Molly F., additional, and Ivers, Louise C., additional
- Published
- 2021
- Full Text
- View/download PDF
17. Development of a qualitative real-time RT-PCR assay for the detection of SARS-CoV-2: a guide and case study in setting up an emergency-use, laboratory-developed molecular microbiological assay
- Author
-
Anahtar, Melis N, primary, Shaw, Bennett M, additional, Slater, Damien, additional, Byrne, Elizabeth H, additional, Botti-Lodovico, Yolanda, additional, Adams, Gordon, additional, Schaffner, Stephen F, additional, Eversley, Jacqueline, additional, McGrath, Graham E G, additional, Gogakos, Tasos, additional, Lennerz, Jochen, additional, Marble, Hetal Desai, additional, Ritterhouse, Lauren L, additional, Batten, Julie M, additional, Georgantas, N Zeke, additional, Pellerin, Rebecca, additional, Signorelli, Sylvia, additional, Thierauf, Julia, additional, Kemball, Molly, additional, Happi, Christian, additional, Grant, Donald S, additional, Ndiaye, Daouda, additional, Siddle, Katherine J, additional, Mehta, Samar B, additional, Harris, Jason B, additional, Ryan, Edward T, additional, Pierce, Virginia M, additional, LaRocque, Regina C, additional, Lemieux, Jacob E, additional, Sabeti, Pardis C, additional, Rosenberg, Eric S, additional, Branda, John A, additional, and Turbett, Sarah E, additional
- Published
- 2021
- Full Text
- View/download PDF
18. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Juba, South Sudan: a population-based study
- Author
-
Wiens, Kirsten E., primary, Mawien, Pinyi Nyimol, additional, Rumunu, John, additional, Slater, Damien, additional, Jones, Forrest K., additional, Moheed, Serina, additional, Caflish, Andrea, additional, Bior, Bior K., additional, Jacob, Iboyi Amanya, additional, Lako, Richard Lino Loro, additional, Guyo, Argata Guracha, additional, Olu, Olushayo Oluseun, additional, Maleghemi, Sylvester, additional, Baguma, Andrew, additional, Hassen, Juma John, additional, Baya, Sheila K., additional, Deng, Lul, additional, Lessler, Justin, additional, Demby, Maya N., additional, Sanchez, Vanessa, additional, Mills, Rachel, additional, Fraser, Clare, additional, Charles, Richelle C., additional, Harris, Jason B., additional, Azman, Andrew S., additional, and Wamala, Joseph F., additional
- Published
- 2021
- Full Text
- View/download PDF
19. Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events
- Author
-
Lemieux, Jacob E., primary, Siddle, Katherine J., additional, Shaw, Bennett M., additional, Loreth, Christine, additional, Schaffner, Stephen F., additional, Gladden-Young, Adrianne, additional, Adams, Gordon, additional, Fink, Timelia, additional, Tomkins-Tinch, Christopher H., additional, Krasilnikova, Lydia A., additional, DeRuff, Katherine C., additional, Rudy, Melissa, additional, Bauer, Matthew R., additional, Lagerborg, Kim A., additional, Normandin, Erica, additional, Chapman, Sinéad B., additional, Reilly, Steven K., additional, Anahtar, Melis N., additional, Lin, Aaron E., additional, Carter, Amber, additional, Myhrvold, Cameron, additional, Kemball, Molly E., additional, Chaluvadi, Sushma, additional, Cusick, Caroline, additional, Flowers, Katelyn, additional, Neumann, Anna, additional, Cerrato, Felecia, additional, Farhat, Maha, additional, Slater, Damien, additional, Harris, Jason B., additional, Branda, John A., additional, Hooper, David, additional, Gaeta, Jessie M., additional, Baggett, Travis P., additional, O’Connell, James, additional, Gnirke, Andreas, additional, Lieberman, Tami D., additional, Philippakis, Anthony, additional, Burns, Meagan, additional, Brown, Catherine M., additional, Luban, Jeremy, additional, Ryan, Edward T., additional, Turbett, Sarah E., additional, LaRocque, Regina C., additional, Hanage, William P., additional, Gallagher, Glen R., additional, Madoff, Lawrence C., additional, Smole, Sandra, additional, Pierce, Virginia M., additional, Rosenberg, Eric, additional, Sabeti, Pardis C., additional, Park, Daniel J., additional, and MacInnis, Bronwyn L., additional
- Published
- 2021
- Full Text
- View/download PDF
20. Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients
- Author
-
Iyer, Anita S., primary, Jones, Forrest K., additional, Nodoushani, Ariana, additional, Kelly, Meagan, additional, Becker, Margaret, additional, Slater, Damien, additional, Mills, Rachel, additional, Teng, Erica, additional, Kamruzzaman, Mohammad, additional, Garcia-Beltran, Wilfredo F., additional, Astudillo, Michael, additional, Yang, Diane, additional, Miller, Tyler E., additional, Oliver, Elizabeth, additional, Fischinger, Stephanie, additional, Atyeo, Caroline, additional, Iafrate, A. John, additional, Calderwood, Stephen B., additional, Lauer, Stephen A., additional, Yu, Jingyou, additional, Li, Zhenfeng, additional, Feldman, Jared, additional, Hauser, Blake M., additional, Caradonna, Timothy M., additional, Branda, John A., additional, Turbett, Sarah E., additional, LaRocque, Regina C., additional, Mellon, Guillaume, additional, Barouch, Dan H., additional, Schmidt, Aaron G., additional, Azman, Andrew S., additional, Alter, Galit, additional, Ryan, Edward T, additional, Harris, Jason B., additional, and Charles, Richelle C., additional
- Published
- 2020
- Full Text
- View/download PDF
21. Development of a qualitative real-time RT-PCR assay for the detection of SARS-CoV-2: A guide and case study in setting up an emergency-use, laboratory-developed molecular assay
- Author
-
Anahtar, Melis N., primary, Shaw, Bennett, additional, Slater, Damien, additional, Byrne, Elizabeth, additional, Botti-Lodovico, Yolanda, additional, Adams, Gordon, additional, Schaffner, Stephen, additional, Eversley, Jacqueline, additional, McGrath, Graham, additional, Gogakos, Tasos, additional, Lennerz, Jochen, additional, Marble, Hetal Desai, additional, Ritterhouse, Lauren L., additional, Batten, Julie, additional, Georgantas, N. Zeke, additional, Pellerin, Rebecca, additional, Signorelli, Sylvia, additional, Thierauf, Julia, additional, Kemball, Molly, additional, Happi, Christian, additional, Grant, Donald S., additional, Ndiaye, Daouda, additional, Siddle, Katherine J., additional, Mehta, Samar B., additional, Harris, Jason, additional, Ryan, Edward T., additional, Pierce, Virginia, additional, LaRocque, Regina, additional, Lemieux, Jacob E., additional, Sabeti, Pardis, additional, Rosenberg, Eric, additional, Branda, John, additional, and Turbett, Sarah E., additional
- Published
- 2020
- Full Text
- View/download PDF
22. Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events
- Author
-
Lemieux, Jacob E., primary, Siddle, Katherine J., additional, Shaw, Bennett M., additional, Loreth, Christine, additional, Schaffner, Stephen F., additional, Gladden-Young, Adrianne, additional, Adams, Gordon, additional, Fink, Timelia, additional, Tomkins-Tinch, Christopher H., additional, Krasilnikova, Lydia A., additional, DeRuff, Katherine C., additional, Rudy, Melissa, additional, Bauer, Matthew R., additional, Lagerborg, Kim A., additional, Normandin, Erica, additional, Chapman, Sinead B., additional, Reilly, Steven K., additional, Anahtar, Melis N., additional, Lin, Aaron E., additional, Carter, Amber, additional, Myhrvold, Cameron, additional, Kemball, Molly E., additional, Chaluvadi, Sushma, additional, Cusick, Caroline, additional, Flowers, Katelyn, additional, Neumann, Anna, additional, Cerrato, Felecia, additional, Farhat, Maha, additional, Slater, Damien, additional, Harris, Jason B., additional, Branda, John, additional, Hooper, David, additional, Gaeta, Jessie M., additional, Baggett, Travis P., additional, O’Connell, James, additional, Gnirke, Andreas, additional, Lieberman, Tami D., additional, Philippakis, Anthony, additional, Burns, Meagan, additional, Brown, Catherine M., additional, Luban, Jeremy, additional, Ryan, Edward T., additional, Turbett, Sarah E., additional, LaRocque, Regina C., additional, Hanage, William P., additional, Gallagher, Glen R., additional, Madoff, Lawrence C., additional, Smole, Sandra, additional, Pierce, Virginia M., additional, Rosenberg, Eric, additional, Sabeti, Pardis C., additional, Park, Daniel J., additional, and Maclnnis, Bronwyn L., additional
- Published
- 2020
- Full Text
- View/download PDF
23. Dynamics and significance of the antibody response to SARS-CoV-2 infection
- Author
-
Iyer, Anita S., primary, Jones, Forrest K., additional, Nodoushani, Ariana, additional, Kelly, Meagan, additional, Becker, Margaret, additional, Slater, Damien, additional, Mills, Rachel, additional, Teng, Erica, additional, Kamruzzaman, Mohammad, additional, Garcia-Beltran, Wilfredo F., additional, Astudillo, Michael, additional, Yang, Diane, additional, Miller, Tyler E., additional, Oliver, Elizabeth, additional, Fischinger, Stephanie, additional, Atyeo, Caroline, additional, Iafrate, A. John, additional, Calderwood, Stephen B., additional, Lauer, Stephen A., additional, Yu, Jingyou, additional, Li, Zhenfeng, additional, Feldman, Jared, additional, Hauser, Blake M., additional, Caradonna, Timothy M., additional, Branda, John A., additional, Turbett, Sarah E., additional, LaRocque, Regina C., additional, Mellon, Guillaume, additional, Barouch, Dan H., additional, Schmidt, Aaron G., additional, Azman, Andrew S., additional, Alter, Galit, additional, Ryan, Edward T, additional, Harris, Jason B., additional, and Charles, Richelle C., additional
- Published
- 2020
- Full Text
- View/download PDF
24. Antibody Responses after COVID-19 Infection in Patients Who Are Mildly Symptomatic or Asymptomatic in Bangladesh
- Author
-
Shirin, Tahmina, primary, Bhuiyan, Taufiqur R., additional, Charles, Richelle C., additional, Amin, Shaheena, additional, Bhuiyan, Imran, additional, Kawser, Zannat, additional, Rahat, Asifuzaman, additional, Alam, Ahmed Nawsher, additional, Sultana, Sharmin, additional, Aleem, Md Abdul, additional, Khan, Manjur Hossain, additional, Khan, Samsad Rabbani, additional, LaRocque, Regina C., additional, Calderwood, Stephen B., additional, Ryan, Edward T., additional, Slater, Damien M., additional, Banu, Sayera, additional, Clemens, John D., additional, Harris, Jason B., additional, Flora, Meerjady Sabrina, additional, and Qadri, Firdausi, additional
- Published
- 2020
- Full Text
- View/download PDF
25. Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 IgG in Juba, South Sudan, 20201.
- Author
-
Wiens, Kirsten E., Mawien, Pinyi Nyimol, Rumunu, John, Slater, Damien, Jones, Forrest K., Moheed, Serina, Caflisch, Andrea, Bior, Bior K., Jacob, Iboyi Amanya, Lako, Richard Lino, Guyo, Argata Guracha, Olu, Olushayo Oluseun, Maleghemi, Sylvester, Baguma, Andrew, Hassen, Juma John, Baya, Sheila K., Lul Deng, Lessler, Justin, Demby, Maya N., and Sanchez, Vanessa
- Subjects
COVID-19 ,COVID-19 pandemic ,SARS-CoV-2 ,SEROPREVALENCE ,SERODIAGNOSIS - Abstract
Relatively few coronavirus disease cases and deaths have been reported from sub-Saharan Africa, although the extent of its spread remains unclear. During August 10-September 11, 2020, we recruited 2,214 participants for a representative household-based cross-sectional serosurvey in Juba, South Sudan. We found 22.3% of participants had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain IgG titers above prepandemic levels. After accounting for waning antibody levels, age, and sex, we estimated that 38.3% (95% credible interval 31.8%-46.5%) of the population had been infected with SARS-CoV-2. At this rate, for each PCR-confirmed SARS-CoV-2 infection reported by the Ministry of Health, 103 (95% credible interval 86-126) infections would have been unreported, meaning SARS-CoV-2 has likely spread extensively within Juba. We also found differences in background reactivity in Juba compared with Boston, Massachusetts, USA, where the immunoassay was validated. Our findings underscore the need to validate serologic tests in sub-Saharan Africa populations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
26. Abstract 3647: Multiplex digital PCR analysis of EGFR mutations for lung cancer characterization and monitoring
- Author
-
Samuels, Michael L., primary, Read, Christina, additional, Jackson, Jennifer, additional, Slater, Damien, additional, Chappell, David, additional, and Consugar, Mark, additional
- Published
- 2016
- Full Text
- View/download PDF
27. Replication licensing promotes cyclin D1 expression and G 1 progression in untransformed human cells
- Author
-
Vaziri, Cyrus, Cook, Jeanette Gowen, Nevis, Kathleen, Slater, Damien M., Liu, Peijun, and Lenburg, Marc
- Abstract
Defects in DNA replication are implicated as early and causal events in malignancy. However, the immediate effects of impaired DNA replication licensing on cell cycle progression of non-malignant human cells are unknown. Therefore, we have investigated the acute effects of Mcm7 ablation using synchronized cultures of untransformed Human Dermal Fibroblasts (HDF). Mcm7 ablation elicited a G1 delay associated with impaired activation of CDK4 and CDK2 and reduced Rb phosphorylation. The cell cycle delay of Mcm7-ablated cells was not associated with a DNA damage response. However, levels of cyclin D1 mRNA were specifically reduced and binding of RNA Polymerase II to the CYCD1 promoter was decreased in Mcm7-depleted cells. Similar to Mcm7-deficiency, Mcm2- or Cdc6-depletion led to impaired cyclin D expression. Ectopic overexpression of Cdc6 in quiescent cells promoted cyclin D1 expression, CDK4 activation and G1 progression. Therefore timely and efficient expression of cyclin D1 during G1 phase requires replication licensing. Reconstitution of cyclin D1 expression was insufficient to correct the G1 delay of Mcm7-depleted cells, indicating that additional cell cycle events during G1 are dependent on replication licensing. However, ectopic expression of the HPV-E7 oncoprotein, and the resulting bypass of the requirement for cyclin D1-Rb signaling enabled Mcm7-depleted cells to enter S-phase. HPV-E7-induced S-phase entry of Mcm7-depleted cells led to a DNA damage response, a hallmark of pre-malignancy. Taken together, our results suggest the existence of a ‘replication licensing restriction point’ that couples pre-RC assembly with G1 progression in normal cells to minimize replication stress, DNA damage and tumorigenesis.
- Published
- 2009
- Full Text
- View/download PDF
28. Replication licensing promotes cyclin D1 expression and G1progression in untransformed human cells
- Author
-
Liu, Peijun, primary, Slater, Damien M., additional, Lenburg, Marc, additional, Nevis, Kathleen, additional, Cook, Jeanette Gowan, additional, and Vaziri, Cyrus, additional
- Published
- 2009
- Full Text
- View/download PDF
29. The Chk1-mediated S-phase Checkpoint Targets Initiation Factor Cdc45 via a Cdc25A/Cdk2-independent Mechanism
- Author
-
Liu, Peijun, primary, Barkley, Laura R., additional, Day, Tovah, additional, Bi, Xiaohui, additional, Slater, Damien M., additional, Alexandrow, Mark G., additional, Nasheuer, Heinz-Peter, additional, and Vaziri, Cyrus, additional
- Published
- 2006
- Full Text
- View/download PDF
30. Rad18 Regulates DNA Polymerase κ and Is Required for Recovery from S-Phase Checkpoint-Mediated Arrest
- Author
-
Bi, Xiaohui, primary, Barkley, Laura R., additional, Slater, Damien M., additional, Tateishi, Satoshi, additional, Yamaizumi, Masaru, additional, Ohmori, Haruo, additional, and Vaziri, Cyrus, additional
- Published
- 2006
- Full Text
- View/download PDF
31. DNA Polymerase κ Is Specifically Required for Recovery from the Benzo[a]pyrene-Dihydrodiol Epoxide (BPDE)-induced S-phase Checkpoint
- Author
-
Bi, Xiaohui, primary, Slater, Damien M., additional, Ohmori, Haruo, additional, and Vaziri, Cyrus, additional
- Published
- 2005
- Full Text
- View/download PDF
32. TorsinA in PC12 cells: Localization in the endoplasmic reticulum and response to stress
- Author
-
Hewett, Jeffrey, primary, Ziefer, Philipp, additional, Bergeron, Daniele, additional, Naismith, Teri, additional, Boston, Heather, additional, Slater, Damien, additional, Wilbur, Jeremy, additional, Schuback, Deborah, additional, Kamm, Christoph, additional, Smith, Nicole, additional, Camp, Sara, additional, Ozelius, Laurie J., additional, Ramesh, Vijaya, additional, Hanson, Phyllis I., additional, and Breakefield, Xandra O., additional
- Published
- 2003
- Full Text
- View/download PDF
33. Replication licensing promotes cyclin D1 expression and G1 progression in untransformed human cells.
- Author
-
Liu, Peijun, Slater, Damien M., Lenburg, Marc, Nevis, Kathleen, Cook, Jeanette Gowen, and Vaziri, Cyrus
- Published
- 2009
- Full Text
- View/download PDF
34. Rad18 Regulates DNA Polymerase κ and Is Required for Recovery from S-Phase Checkpoint-Mediated Arrest.
- Author
-
Xiaohui Bi, Barkley, Laura R., Slater, Damien M., Tateishi, Satoshi, Yamaizumi, Masaru, Ohmori, Haruo, and Vaziri, Cyrus
- Subjects
DNA polymerases ,DNA replication ,GENETIC toxicology ,UBIQUITIN ,RNA ,LIGASES - Abstract
We have investigated mechanisms that recruit the translesion synthesis (TLS) DNA polymerase Pol κ to stalled replication forks. The DNA polymerase processivity factor PCNA is monoubiquitinated and interacts with Pol κ in cells treated with the bulky adduct-forming genotoxin benzo[a]pyrene dihydrodiol epoxide (BPDE). A monoubiquitination-defective mutant form of PCNA fails to interact with Pol κ. Small interfering RNA-mediated downregulation of the E3 ligase Rad18 inhibits BPDE-induced PCNA ubiquitination and association between PCNA and Pol κ. Conversely, overexpressed Rad18 induces PCNA ubiquitination and association between PCNA and Pol κ in a DNA damage-independent manner. Therefore, association of Pol κ with PCNA is regulated by Rad18-mediated PCNA ubiquitination. Cells from Rad18
-/- transgenic mice show defective recovery from BPDE-induced S-phase checkpoints. In Rad18-/- cells, BPDE induces elevated and persistent activation of checkpoint kinases, indicating persistently stalled forks due to defective TLS. Rad18-deficient cells show reduced viability after BPDE challenge compared with wild-type cells (but survival after hydroxyurea or ionizing radiation treatment is unaffected by Rad18 deficiency). Inhibition of RPA/ATR/Chk1-mediated S-phase checkpoint signaling partially inhibited BPDE-induced PCNA ubiquitination and prevented interactions between PCNA and Pol κ. Taken together, our results indicate that ATR/Chk1 signaling is required for Rad18-mediated PCNA monoubiquitination. Recruitment of Pol κ to ubiquitinated PCNA enables lesion bypass and eliminates stalled forks, thereby attenuating the S-phase checkpoint. [ABSTRACT FROM AUTHOR]- Published
- 2006
- Full Text
- View/download PDF
35. Reemergence of Cholera in Haiti.
- Author
-
Boney, Jacques, Ivers, Louise C., Waldor, Matthew K., Rubin, Daniel H F, Zingl, Franz G, Leitner, Deborah R, Ternier, Ralph, Compere, Valusnor, Marseille, Samson, Slater, Damien, Harris, Jason B, Chowdhury, Fahima, Qadri, Firdausi, and Boncy, Jacques
- Subjects
- *
CHOLERA - Abstract
The article discusses research on the possible origins of the 2022 resurgence of cholera in Haiti. Topics explored include the genomic and phenotypic analysis of a Vibrio cholerae strain isolated from a stool sample obtained from a cholera patient, the similarity observed in the phenotypes of the 2010 and 2022 bacteria strains, and the factors which may have contributed to the 2022 outbreak such as waning population immunity and poor sanitation.
- Published
- 2022
- Full Text
- View/download PDF
36. Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 IgG in Juba, South Sudan, 20201.
- Author
-
Wiens, Kirsten E., Mawien, Pinyi Nyimol, Rumunu, John, Slater, Damien, Jones, Forrest K., Moheed, Serina, Caflisch, Andrea, Bior, Bior K., Jacob, Iboyi Amanya, Lako, Richard Lino, Guyo, Argata Guracha, Olu, Olushayo Oluseun, Maleghemi, Sylvester, Baguma, Andrew, Hassen, Juma John, Baya, Sheila K., Lul Deng, Lessler, Justin, Demby, Maya N., and Sanchez, Vanessa
- Subjects
- *
COVID-19 , *COVID-19 pandemic , *SARS-CoV-2 , *SEROPREVALENCE , *SERODIAGNOSIS - Abstract
Relatively few coronavirus disease cases and deaths have been reported from sub-Saharan Africa, although the extent of its spread remains unclear. During August 10-September 11, 2020, we recruited 2,214 participants for a representative household-based cross-sectional serosurvey in Juba, South Sudan. We found 22.3% of participants had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain IgG titers above prepandemic levels. After accounting for waning antibody levels, age, and sex, we estimated that 38.3% (95% credible interval 31.8%-46.5%) of the population had been infected with SARS-CoV-2. At this rate, for each PCR-confirmed SARS-CoV-2 infection reported by the Ministry of Health, 103 (95% credible interval 86-126) infections would have been unreported, meaning SARS-CoV-2 has likely spread extensively within Juba. We also found differences in background reactivity in Juba compared with Boston, Massachusetts, USA, where the immunoassay was validated. Our findings underscore the need to validate serologic tests in sub-Saharan Africa populations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
37. The Chk1 -mediated S-phase Checkpoint Targets Initiation Factor Cdc45 via a Cdc25A/Cdk2-independent Mechanism.
- Author
-
Peijun Liu, Barkley, Laura R., Day, Tovah, Xiaohui Bi, Slater, Damien M., Alexandrow, Mark G., Nasheuer, Heinz-Peter, and Vaziri, Cyrus
- Subjects
- *
DNA damage , *CARCINOGENS , *DNA synthesis , *DNA replication , *CHROMATIN - Abstract
DNA damage induced by the carcinogen benzo[a]pyrene dihydrodiol epoxide (BPDE) induces a Chk1-dependent S-phase checkpoint. Here, we have investigated the molecular basis of BPDE-induced S-phase arrest. Chk1-dependent inhibition of DNA synthesis in BPDE-treated cells occurred without detectable changes in Cdc25A levels, Cdk2 activity, or Cdc7/Dbf4 interaction. Overexpression studies showed that Cdc25A, cyclin A/Cdk2, and Cdc7/Dbf4 were not rate-limiting for DNA synthesis when the BPDE-induced S-phase checkpoint was active. To investigate other potential targets of the S-phase checkpoint, we tested the effects of BPDE on the chromatin association of DNA replication factors. The levels of chromatin- associated Cdc45 (but not soluble Cdc45) were reduced concomitantly with BPDE-induced Chk1 activation and inhibition of DNA synthesis. The chromatin association of Mcm7, Mcm10, and proliferating cell nuclear antigen was unaffected by BPDE treatment. However, the association between Mcm7 and Cdc45 in the chromatin fraction was inhibited in BPDE-treated cells. Chromatin immunoprecipitation analyses demonstrated reduced association of Cdc45 with the β-globin origin of replication in BPDE-treated cells. The inhibitory effects of BPDE on DNA synthesis, Cdc45/Mcm7 associations, and interactions between Cdc45 and the β-globin locus were abrogated by the Chkl inhibitor UCN-O1. Taken together, our results show that the association between Cdc45 and Mcm7 at origins of replication is negatively regulated by Chk1 in a Cdk2-independent manner, Therefore, Cdc45 is likely to be an important target of the Chk1-mediated S-phase checkpoint. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
38. Multiplexed real-time PCR for the detection and differentiation of Klebsiella pneumoniae O-antigen serotypes.
- Author
-
Slater D, Hutt Vater K, Sridhar S, Hwang W, Bielawski D, Turbett SE, LaRocque RC, and Harris JB
- Subjects
- Humans, Multiplex Polymerase Chain Reaction methods, Whole Genome Sequencing, Klebsiella pneumoniae genetics, Klebsiella pneumoniae isolation & purification, Klebsiella pneumoniae classification, Klebsiella pneumoniae immunology, O Antigens genetics, O Antigens immunology, O Antigens analysis, Klebsiella Infections diagnosis, Klebsiella Infections microbiology, Real-Time Polymerase Chain Reaction methods, Feces microbiology, Serogroup, Serotyping methods
- Abstract
Klebsiella pneumoniae has emerged as a global health threat due to its role in the spread of antimicrobial resistance and because it is a frequent cause of hospital-acquired infections and neonatal sepsis. Capsular and lipopolysaccharide (LPS) O-antigen polysaccharide surface antigens are major immunogens that are useful for strain classification and are candidates for vaccine development. We have developed real-time PCR reagents for molecular serotyping, subtyping, and quantitation of the most prevalent LPS O-antigen types (i.e., O1, O2, O3, and O5) of Klebsiella pneumoniae . We describe two applications for this O-typing assay: for screening culture isolates and for direct typing of Klebsiella pneumoniae present in stool samples. We find 100% concordance between the results of the O-typing assay and whole-genome sequencing of 81 culture isolates, and >90% agreement in O-typing performed directly on specimens of human stool, with disagreement arising primarily from a lack of sensitivity of the culture-based comparator method. Additionally, we find evidence for mixed O-type populations at varying levels of abundance in direct tests of stool from a hospitalized patient population. Taken together, these results demonstrate that this novel O-typing assay can be a useful tool for K. pneumoniae epidemiologic and vaccine studies.IMPORTANCE Klebsiella pneumoniae is an important opportunistic pathogen. The gastrointestinal (GI) tract is the primary reservoir of K. pneumoniae in humans, and GI carriage is believed to be a prerequisite for invasive infection. Knowledge about the dynamics and duration of GI carriage has been hampered by the lack of tools suitable for detection and strain discrimination. Real-time PCR is particularly suited to the higher-throughput workflows used in population-based studies, which are needed to improve our understanding of carriage dynamics and the factors influencing K. pneumoniae colonization., Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
- Full Text
- View/download PDF
39. Antibody responses in Klebsiella pneumoniae bloodstream infection: a cohort study.
- Author
-
Hwang W, Wantuch PL, Bernshtein B, Zhiteneva J, Slater D, Vater KH, Sridhar S, Oliver E, Roach DJ, Rao S, Turbett SE, Knoot CJ, Harding CM, Amin MN, Cross AS, LaRocque RC, Rosen DA, and Harris JB
- Abstract
Background: Klebsiella pneumonia (Kpn) is the fourth leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive Kpn. In this study, we sought to determine whether the O-specific polysaccharide (OPS) antigen, a vaccine candidate, is immunogenic in humans with Kpn bloodstream infection (BSI). We also sought to define the cross-reactivity of human antibody responses among structurally related Kpn OPS subtypes and to assess the impact of capsule production on OPS-targeted antibody binding and function., Methods: We measured plasma antibody responses to OPS (and MrkA, a fimbrial protein) in a cohort of patients with Kpn BSI and compared these with controls, including a cohort of healthy individuals and a cohort of individuals with Enterococcus BSI. We performed flow cytometry to measure the impact of Kpn capsule production on whole cell antibody binding and complement deposition, utilizing patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates., Findings: We enrolled 69 patients with Kpn BSI. Common OPS serotypes accounted for 57/69 (83%) of infections. OPS was highly immunogenic in patients with Kpn BSI, and peak OPS-IgG antibody responses in patients were 10 to 30-fold higher than antibody levels detected in healthy controls, depending on the serotype. There was significant cross-reactivity among structurally similar OPS subtypes, including the O1v1/O1v2, O2v1/O2v2 and O3/O3b subtypes. Physiological amounts of capsule produced by both hyperencapsulated and non-hyperencapsulated Kpn significantly inhibited OPS-targeted antibody binding and function., Interpretation: OPS was highly immunogenic in patients with Kpn BSI, supporting its potential as a candidate vaccine antigen. The strong cross-reactivity observed between similar OPS subtypes in humans with Kpn BSI suggests that it may not be necessary to include all subtypes in an OPS-based vaccine. However, these observations are tempered by the fact that capsule production, even in non-highly encapsulated strains, has the potential to interfere with OPS antibody binding. This may limit the effectiveness of vaccines that exclusively target OPS., Funding: National Institute of Allergy and Infectious Diseases at the National Institutes of Health., Research in Context: Evidence before this study: Despite the potential of O-specific polysaccharide (OPS) as a vaccine antigen against Klebsiella pneumoniae (Kpn), the immunogenicity of OPS in humans remains largely unstudied, creating a significant knowledge gap with regard to vaccine development. A search of PubMed for publications up to March 18, 2024, using the terms " Klebsiella pneumoniae " and "O-specific polysaccharide" or "O-antigen" or "lipopolysaccharide" revealed no prior studies addressing OPS antibody responses in humans with Kpn bloodstream infections (BSI). One prior study
1 evaluated antibody response to a single lipopolysaccharide (which contains one subtype of OPS) in humans with invasive Kpn infection; however, in this study OPS typing of the infecting strains and target antigen were not described. Added value of this study: Our investigation into OPS immunogenicity in a human cohort marks a significant advance. Analyzing plasma antibody responses in 69 patients with Kpn BSI, we found OPS to be broadly immunogenic across all the types and subtypes examined, and there was significant cross-reactivity among structurally related OPS antigens. We also demonstrated that Kpn capsule production inhibit OPS antibody binding and the activation of complement on the bacterial surface, even in classical Kpn strains expressing lower levels of capsule. Implications of all the available evidence: While the immunogenicity and broad cross-reactivity of OPS in humans with Kpn BSI suggests it is a promising vaccine candidate, the obstruction of OPS antibody binding and engagement by physiologic levels of Kpn capsule underscores the potential limitations of an exclusively OPS-antigen based vaccine for Kpn. Our study provides insights for the strategic development of vaccines aimed at combating Kpn infections, an important antimicrobial resistant pathogen.- Published
- 2024
- Full Text
- View/download PDF
40. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Juba, South Sudan: a population-based study.
- Author
-
Wiens KE, Mawien PN, Rumunu J, Slater D, Jones FK, Moheed S, Caflish A, Bior BK, Jacob IA, Lako RLL, Guyo AG, Olu OO, Maleghemi S, Baguma A, Hassen JJ, Baya SK, Deng L, Lessler J, Demby MN, Sanchez V, Mills R, Fraser C, Charles RC, Harris JB, Azman AS, and Wamala JF
- Abstract
Background: Relatively few COVID-19 cases and deaths have been reported through much of sub-Saharan Africa, including South Sudan, although the extent of SARS-CoV-2 spread remains unclear due to weak surveillance systems and few population-representative serosurveys., Methods: We conducted a representative household-based cross-sectional serosurvey in Juba, South Sudan. We quantified IgG antibody responses to SARS-CoV-2 spike protein receptor-binding domain and estimated seroprevalence using a Bayesian regression model accounting for test performance., Results: We recruited 2,214 participants from August 10 to September 11, 2020 and 22.3% had anti-SARS-CoV-2 IgG titers above levels in pre-pandemic samples. After accounting for waning antibody levels, age, and sex, we estimated that 38.5% (32.1 - 46.8) of the population had been infected with SARS-CoV-2. For each RT-PCR confirmed COVID-19 case, 104 (87-126) infections were unreported. Background antibody reactivity was higher in pre-pandemic samples from Juba compared to Boston, where the serological test was validated. The estimated proportion of the population infected ranged from 30.1% to 60.6% depending on assumptions about test performance and prevalence of clinically severe infections., Conclusions: SARS-CoV-2 has spread extensively within Juba. Validation of serological tests in sub-Saharan African populations is critical to improve our ability to use serosurveillance to understand and mitigate transmission.
- Published
- 2021
- Full Text
- View/download PDF
41. Development of a qualitative real-time RT-PCR assay for the detection of SARS-CoV-2: A guide and case study in setting up an emergency-use, laboratory-developed molecular assay.
- Author
-
Anahtar MN, Shaw B, Slater D, Byrne E, Botti-Lodovico Y, Adams G, Schaffner S, Eversley J, McGrath G, Gogakos T, Lennerz J, Desai Marble H, Ritterhouse LL, Batten J, Georgantas NZ, Pellerin R, Signorelli S, Thierauf J, Kemball M, Happi C, Grant DS, Ndiaye D, Siddle KJ, Mehta SB, Harris J, Ryan ET, Pierce V, LaRocque R, Lemieux JE, Sabeti P, Rosenberg E, Branda J, and Turbett SE
- Abstract
Developing and deploying new diagnostic tests is difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important for an effective response. In the early stages of a pandemic, laboratories play a key role in helping health care providers and public health authorities detect active infection, a task most commonly achieved using nucleic acid-based assays. While the landscape of diagnostics is rapidly evolving, polymerase chain reaction (PCR) remains the gold-standard of nucleic acid-based diagnostic assays, in part due to its reliability, flexibility, and wide deployment. To address a critical local shortage of testing capacity persisting during the COVID-19 outbreak, our hospital set up a molecular based laboratory developed test (LDT) to accurately and safely diagnose SARS-CoV-2. We describe here the process of developing an emergency-use LDT, in the hope that our experience will be useful to other laboratories in future outbreaks and will help to lower barriers to fast and accurate diagnostic testing in crisis conditions.
- Published
- 2020
- Full Text
- View/download PDF
42. Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events.
- Author
-
Lemieux JE, Siddle KJ, Shaw BM, Loreth C, Schaffner SF, Gladden-Young A, Adams G, Fink T, Tomkins-Tinch CH, Krasilnikova LA, DeRuff KC, Rudy M, Bauer MR, Lagerborg KA, Normandin E, Chapman SB, Reilly SK, Anahtar MN, Lin AE, Carter A, Myhrvold C, Kemball ME, Chaluvadi S, Cusick C, Flowers K, Neumann A, Cerrato F, Farhat M, Slater D, Harris JB, Branda J, Hooper D, Gaeta JM, Baggett TP, O'Connell J, Gnirke A, Lieberman TD, Philippakis A, Burns M, Brown CM, Luban J, Ryan ET, Turbett SE, LaRocque RC, Hanage WP, Gallagher GR, Madoff LC, Smole S, Pierce VM, Rosenberg E, Sabeti PC, Park DJ, and Maclnnis BL
- Abstract
SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as of August 1, 2020. To investigate the introduction, spread, and epidemiology of COVID-19 in the Boston area, we sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region, including nearly all confirmed cases within the first week of the epidemic and hundreds of cases from major outbreaks at a conference, a nursing facility, and among homeless shelter guests and staff. The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe. We studied two superspreading events covered by the data, events that led to very different outcomes because of the timing and populations involved. One produced rapid spread in a vulnerable population but little onward transmission, while the other was a major contributor to sustained community transmission, including outbreaks in homeless populations, and was exported to several other domestic and international sites. The same two events differed significantly in the number of new mutations seen, raising the possibility that SARS-CoV-2 superspreading might encompass disparate transmission dynamics. Our results highlight the failure of measures to prevent importation into MA early in the outbreak, underscore the role of superspreading in amplifying an outbreak in a major urban area, and lay a foundation for contact tracing informed by genetic data., Competing Interests: Competing interests: J.E.L. has received consulting fees from Sherlock Biosciences. J.B. has been a consultant for T2 Biosystems, DiaSorin, and Roche Diagnostics. A.P. is a Venture Partner at Google Ventures. P.C.S. is a co-founder and shareholder of Sherlock Biosciences, and a Board member and shareholder of Danaher Corporation.
- Published
- 2020
- Full Text
- View/download PDF
43. Dynamics and significance of the antibody response to SARS-CoV-2 infection.
- Author
-
Iyer AS, Jones FK, Nodoushani A, Kelly M, Becker M, Slater D, Mills R, Teng E, Kamruzzaman M, Garcia-Beltran WF, Astudillo M, Yang D, Miller TE, Oliver E, Fischinger S, Atyeo C, Iafrate AJ, Calderwood SB, Lauer SA, Yu J, Li Z, Feldman J, Hauser BM, Caradonna TM, Branda JA, Turbett SE, LaRocque RC, Mellon G, Barouch DH, Schmidt AG, Azman AS, Alter G, Ryan ET, Harris JB, and Charles RC
- Abstract
Background: Characterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence., Methods: We measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic., Results: Between 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63., Conclusions: Among symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.
- Published
- 2020
- Full Text
- View/download PDF
44. Replication licensing promotes cyclin D1 expression and G1 progression in untransformed human cells.
- Author
-
Liu P, Slater DM, Lenburg M, Nevis K, Cook JG, and Vaziri C
- Subjects
- Cell Cycle Proteins metabolism, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p27 metabolism, DNA Damage, DNA-Binding Proteins deficiency, DNA-Binding Proteins metabolism, Dermis cytology, Down-Regulation, Humans, Minichromosome Maintenance Complex Component 7, Models, Biological, Nuclear Proteins deficiency, Nuclear Proteins metabolism, Papillomavirus E7 Proteins metabolism, Retinoblastoma Protein metabolism, S Phase, Cyclin D1 metabolism, DNA Replication, Fibroblasts cytology, Fibroblasts metabolism, G1 Phase
- Abstract
Defects in DNA replication are implicated as early and causal events in malignancy. However, the immediate effects of impaired DNA replication licensing on cell cycle progression of non-malignant human cells are unknown. Therefore, we have investigated the acute effects of Mcm7 ablation using synchronized cultures of untransformed Human Dermal Fibroblasts (HDF). Mcm7 ablation elicited a G(1) delay associated with impaired activation of CDK4 and CDK2 and reduced Rb phosphorylation. The cell cycle delay of Mcm7-ablated cells was not associated with a DNA damage response. However, levels of cyclin D1 mRNA were specifically reduced and binding of RNA Polymerase II to the CYCD1 promoter was decreased in Mcm7-depleted cells. Similar to Mcm7-deficiency, Mcm2- or Cdc6-depletion led to impaired cyclin D expression. Ectopic overexpression of Cdc6 in quiescent cells promoted cyclin D1 expression, CDK4 activation and G(1) progression. Therefore timely and efficient expression of cyclin D1 during G(1) phase requires replication licensing. Reconstitution of cyclin D1 expression was insufficient to correct the G(1) delay of Mcm7-depleted cells, indicating that additional cell cycle events during G(1) are dependent on replication licensing. However, ectopic expression of the HPV-E7 oncoprotein, and the resulting bypass of the requirement for cyclin D1-Rb signaling enabled Mcm7-depleted cells to enter S-phase. HPV-E7-induced S-phase entry of Mcm7-depleted cells led to a DNA damage response, a hallmark of pre-malignancy. Taken together, our results suggest the existence of a 'replication licensing restriction point' that couples pre-RC assembly with G(1) progression in normal cells to minimize replication stress, DNA damage and tumorigenesis.
- Published
- 2009
- Full Text
- View/download PDF
45. Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest.
- Author
-
Bi X, Barkley LR, Slater DM, Tateishi S, Yamaizumi M, Ohmori H, and Vaziri C
- Subjects
- 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide toxicity, Animals, Ataxia Telangiectasia Mutated Proteins, Carcinogens toxicity, Cell Cycle Proteins metabolism, Cells, Cultured, Checkpoint Kinase 1, DNA-Binding Proteins genetics, Green Fluorescent Proteins analysis, Humans, Mice, Mice, Transgenic, Protein Kinases metabolism, Protein Serine-Threonine Kinases metabolism, S Phase drug effects, S Phase genetics, Ubiquitin-Protein Ligases, DNA Replication drug effects, DNA Replication genetics, DNA-Binding Proteins physiology, DNA-Directed DNA Polymerase metabolism, Proliferating Cell Nuclear Antigen metabolism, Ubiquitin metabolism
- Abstract
We have investigated mechanisms that recruit the translesion synthesis (TLS) DNA polymerase Polkappa to stalled replication forks. The DNA polymerase processivity factor PCNA is monoubiquitinated and interacts with Polkappa in cells treated with the bulky adduct-forming genotoxin benzo[a]pyrene dihydrodiol epoxide (BPDE). A monoubiquitination-defective mutant form of PCNA fails to interact with Polkappa. Small interfering RNA-mediated downregulation of the E3 ligase Rad18 inhibits BPDE-induced PCNA ubiquitination and association between PCNA and Polkappa. Conversely, overexpressed Rad18 induces PCNA ubiquitination and association between PCNA and Polkappa in a DNA damage-independent manner. Therefore, association of Polkappa with PCNA is regulated by Rad18-mediated PCNA ubiquitination. Cells from Rad18(-/-) transgenic mice show defective recovery from BPDE-induced S-phase checkpoints. In Rad18(-/-) cells, BPDE induces elevated and persistent activation of checkpoint kinases, indicating persistently stalled forks due to defective TLS. Rad18-deficient cells show reduced viability after BPDE challenge compared with wild-type cells (but survival after hydroxyurea or ionizing radiation treatment is unaffected by Rad18 deficiency). Inhibition of RPA/ATR/Chk1-mediated S-phase checkpoint signaling partially inhibited BPDE-induced PCNA ubiquitination and prevented interactions between PCNA and Polkappa. Taken together, our results indicate that ATR/Chk1 signaling is required for Rad18-mediated PCNA monoubiquitination. Recruitment of Polkappa to ubiquitinated PCNA enables lesion bypass and eliminates stalled forks, thereby attenuating the S-phase checkpoint.
- Published
- 2006
- Full Text
- View/download PDF
46. DNA polymerase kappa is specifically required for recovery from the benzo[a]pyrene-dihydrodiol epoxide (BPDE)-induced S-phase checkpoint.
- Author
-
Bi X, Slater DM, Ohmori H, and Vaziri C
- Subjects
- 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide pharmacology, Adenoviridae genetics, Animals, Bacterial Proteins, Caffeine pharmacology, Carcinogens, Cell Line, Cell Line, Tumor, Cell Nucleus metabolism, DNA metabolism, DNA Damage, DNA-Directed DNA Polymerase metabolism, Fibroblasts metabolism, Green Fluorescent Proteins metabolism, Humans, Immunoblotting, Luminescent Proteins, Mice, Mice, Transgenic, Microscopy, Fluorescence, Mutagens, Phosphorylation, Recombinant Fusion Proteins metabolism, Signal Transduction, Time Factors, Ultraviolet Rays, DNA-Directed DNA Polymerase physiology, S Phase drug effects
- Abstract
Previously we identified an intra-S-phase cell cycle checkpoint elicited by the DNA-damaging carcinogen benzo[a]pyrene-dihydrodiol epoxide (BPDE). Here we have investigated the roles of lesion bypass DNA polymerases polkappa and poleta in the BPDE-induced S-phase checkpoint. BPDE treatment induced the re-localization of an ectopically expressed green fluorescent protein-polkappa fusion protein to nuclear foci containing sites of active DNA synthesis in human lung carcinoma H1299 cells. In contrast, a similarly expressed yellow fluorescent protein-poleta fusion protein showed a constitutive nuclear focal distribution at replication forks (in the same cells) that was unchanged in response to BPDE. BPDE-induced formation of green fluorescent protein-polkappa nuclear foci was temporally coincident with checkpoint-mediated S-phase arrest. Unlike "wild-type" cells, Polk(-/-) mouse embryonic fibroblasts (MEFs) failed to recover from BPDE-induced S-phase arrest, while exhibiting normal recovery from S-phase arrest induced by ionizing radiation and hydroxyurea. XPV fibroblasts lacking poleta showed a normal S-phase checkpoint response to BPDE (but failed to recover from the UV light-induced S-phase checkpoint), in sharp contrast to Polk(-/-) MEFs. The persistent S-phase arrest in BPDE-treated Polk(-/-) cells was associated with increased levels of histone gammaH2AX (a marker of DNA double-strand breaks (DSBs)) and activation of the DSB-responsive kinases ATM and Chk2. These data suggest that in the absence of polkappa, replication forks stall at sites of damage and collapse and generate DSBs. Therefore, we conclude that the trans-lesion synthesis enzyme polkappa is specifically required for normal recovery from the BPDE-induced S-phase checkpoint.
- Published
- 2005
- Full Text
- View/download PDF
47. TorsinA and early-onset torsion dystonia.
- Author
-
Bragg DC, Slater DJ, and Breakefield XO
- Subjects
- Adenosine Triphosphate metabolism, Age of Onset, Animals, Carrier Proteins genetics, Cell Line metabolism, Cell Line ultrastructure, Gene Products, gag metabolism, Humans, Immunohistochemistry, Inclusion Bodies metabolism, Microscopy, Immunoelectron, Molecular Chaperones metabolism, Mutation, Neurons cytology, Neurons metabolism, Neurons virology, Transfection, Carrier Proteins metabolism, Dystonia Musculorum Deformans metabolism
- Published
- 2004
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.