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Institution

Boston Children's Hospital

HealthcareBoston, Massachusetts, United States
About: Boston Children's Hospital is a healthcare organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 165409 authors who have published 215589 publications receiving 6885627 citations.


Papers
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Journal ArticleDOI
TL;DR: In its last meeting in Jackson Hole, Wyo, after 3 days of intense scientific presentations and discussions, the committee has updated the classification of PID, as reported in this article.
Abstract: Primary immunodeficiency diseases (PIDs) are a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, and T and B lymphocytes. The study of these diseases has provided essential insights into the functioning of the immune system. More than 120 distinct genes have been identified, whose abnormalities account for more than 150 different forms of PID. The complexity of the genetic,immunologic, and clinical features of PID has prompted the need for their classification, with the ultimate goal of facilitating diagnosis and treatment. To serve this goal, an international committee of experts has met every 2 years since 1970. In its last meeting in Jackson Hole, Wyo, after 3 days of intense scientific presentations and discussions, the committee has updated the classification of PID, as reported in this article.

592 citations

Journal ArticleDOI
15 Mar 2017-Nature
TL;DR: It is reported that methylation at the 6 position of adenosine (m6A) in RNA is rapidly and transiently induced at DNA damage sites in response to ultraviolet irradiation, uncovering a novel function for RNA m6A modification in the ultraviolet-induced DNA damage response.
Abstract: Cell proliferation and survival require the faithful maintenance and propagation of genetic information, which are threatened by the ubiquitous sources of DNA damage present intracellularly and in the external environment. A system of DNA repair, called the DNA damage response, detects and repairs damaged DNA and prevents cell division until the repair is complete. Here we report that methylation at the 6 position of adenosine (m6A) in RNA is rapidly (within 2 min) and transiently induced at DNA damage sites in response to ultraviolet irradiation. This modification occurs on numerous poly(A)+ transcripts and is regulated by the methyltransferase METTL3 (methyltransferase-like 3) and the demethylase FTO (fat mass and obesity-associated protein). In the absence of METTL3 catalytic activity, cells showed delayed repair of ultraviolet-induced cyclobutane pyrimidine adducts and elevated sensitivity to ultraviolet, demonstrating the importance of m6A in the ultraviolet-responsive DNA damage response. Multiple DNA polymerases are involved in the ultraviolet response, some of which resynthesize DNA after the lesion has been excised by the nucleotide excision repair pathway, while others participate in trans-lesion synthesis to allow replication past damaged lesions in S phase. DNA polymerase κ (Pol κ), which has been implicated in both nucleotide excision repair and trans-lesion synthesis, required the catalytic activity of METTL3 for immediate localization to ultraviolet-induced DNA damage sites. Importantly, Pol κ overexpression qualitatively suppressed the cyclobutane pyrimidine removal defect associated with METTL3 loss. Thus, we have uncovered a novel function for RNA m6A modification in the ultraviolet-induced DNA damage response, and our findings collectively support a model in which m6A RNA serves as a beacon for the selective, rapid recruitment of Pol κ to damage sites to facilitate repair and cell survival.

592 citations

Journal ArticleDOI
15 Sep 2011-Nature
TL;DR: The identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection is reported and it is found that NPC1 is essential for infection, that it binds to the virus glycoprotein (GP), and that antiviral compounds interfere with GP binding to NPC1.
Abstract: Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection and in many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV. Here we report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection. Using mutant cell lines and informative derivatives of the lead compound, we show that the target of the inhibitor is the endosomal membrane protein Niemann-Pick C1 (NPC1). We find that NPC1 is essential for infection, that it binds to the virus glycoprotein (GP), and that antiviral compounds interfere with GP binding to NPC1. Combined with the results of previous studies of GP structure and function, our findings support a model of EboV infection in which cleavage of the GP1 subunit by endosomal cathepsin proteases removes heavily glycosylated domains to expose the amino-terminal domain, which is a ligand for NPC1 and regulates membrane fusion by the GP2 subunit. Thus, NPC1 is essential for EboV entry and a target for antiviral therapy.

592 citations

Journal ArticleDOI
20 Apr 1990-Science
TL;DR: Immunoprecipitation with antibody to gp120, but not with control immunoglobulin-containing serum, depleted solutions of the viral envelope protein and also prevented both the rise in intracellular calcium and neuronal toxicity, and treatment with calcium channel antagonists may prove useful in mitigating HIV-1-related neuronal injury.
Abstract: Coat protein gp120 from the human immunodeficiency virus type-1 (HIV-1) increased intracellular free calcium and injured rodent retinal ganglion cells and hippocampal neurons in culture. Highly purified recombinant gp120 envelope protein produced these effects in a dose-dependent fashion at picomolar concentrations. Immunoprecipitation with antibody to gp120, but not with control immunoglobulin-containing serum, depleted solutions of the viral envelope protein and also prevented both the rise in intracellular calcium and neuronal toxicity. The gp120-induced increase in intracellular calcium was abrogated by transiently lowering extracellular calcium or by adding the dihydropyridine calcium channel antagonist nimodipine (100 nM). Calcium channel antagonists also prevented gp120-induced neuronal injury. In addition, intracellular stores appeared to contribute substantially to the increase in calcium elicited by gp120. Since increases in intracellular calcium have been associated with neurotoxicity, it is possible that an injurious effect of gp120 on neurons might be related to this mechanism and that treatment with calcium channel antagonists may prove useful in mitigating HIV-1-related neuronal injury.

592 citations

Journal ArticleDOI
TL;DR: Investigation of time trends in the prevalence of asthma and allergic diseases among children living in the eastern part of Germany suggests important differences in the development of atopic disorders.

592 citations


Authors

Showing all 165661 results

NameH-indexPapersCitations
Walter C. Willett3342399413322
Frederick E. Shelton3271485295883
Robert Langer2812324326306
Graham A. Colditz2611542256034
Frank B. Hu2501675253464
George M. Whitesides2401739269833
Eugene Braunwald2301711264576
Ralph B. D'Agostino2261287229636
Mark J. Daly204763304452
Eric B. Rimm196988147119
Virginia M.-Y. Lee194993148820
Bernard Rosner1901162147661
Stuart H. Orkin186715112182
Mark Hallett1861170123741
Ralph Weissleder1841160142508
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202380
2022442
202119,543
202016,558
201913,868
201812,020