Author
Ivanela Kondova
Other affiliations: University of Massachusetts Medical School
Bio: Ivanela Kondova is an academic researcher from Biomedical Primate Research Centre. The author has contributed to research in topics: Immune system & Innate immune system. The author has an hindex of 28, co-authored 80 publications receiving 3606 citations. Previous affiliations of Ivanela Kondova include University of Massachusetts Medical School.
Topics: Immune system, Innate immune system, Virus, Vaccination, Microglia
Papers published on a yearly basis
Papers
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Pompeu Fabra University1, University of Washington2, Stanford University3, University of Michigan4, Harvard University5, University of Arizona6, Max Planck Society7, Aarhus University8, Bilkent University9, University of Minnesota10, University of California, San Francisco11, Autonomous University of Barcelona12, Biomedical Primate Research Centre13, Duke University14, Washington State University15, Franklin & Marshall College16, University of Oxford17, University of Bari18, University of California, San Diego19, University of Copenhagen20, Washington University in St. Louis21, University of Pennsylvania22, National Institutes of Health23, State University of New York System24, Catalan Institution for Research and Advanced Studies25, Copenhagen Zoo26, Howard Hughes Medical Institute27
TL;DR: This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.
Abstract: Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.
807 citations
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TL;DR: Using massively parallel sequencing to compare the microRNA content of human and chimpanzee brains, 447 new miRNA genes are identified, suggesting that evolution of miRNAs is an ongoing process and that along with ancient, highly conserved mi RNAs, there are a number of emerging miRNas.
Abstract: We used massively parallel sequencing to compare the microRNA (miRNA) content of human and chimpanzee brains, and we identified 447 new miRNA genes. Many of the new miRNAs are not conserved beyond primates, indicating their recent origin, and some miRNAs seem species specific, whereas others are expanded in one species through duplication events. These data suggest that evolution of miRNAs is an ongoing process and that along with ancient, highly conserved miRNAs, there are a number of emerging miRNAs.
512 citations
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TL;DR: Both the BCG/MVA.85A prime-boost regime and the novel live attenuated, phoP deficient TB vaccine candidate SO2 showed significant protective efficacy by various parameters in rhesus macaques, which support further development of these primary and combination TB vaccine candidates.
Abstract: The following information was missing from the Funding section: "The study was supported by funding from the NIHR Oxford Biomedical Research Centre programme."
196 citations
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TL;DR: The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.
Abstract: The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. Here we directly compare the efficacies of MVA alone and in combination with classical VV-based vaccines in a cynomolgus macaque monkeypox model. The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.
195 citations
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TL;DR: It is shown that pulmonary BCG prevents infection by using a repeated limiting-dose Mycobacterium tuberculosis challenge model and polyfunctional T-helper type 17 (TH17) cells, interleukin-10 and immunoglobulin A as correlates of local protective immunity.
Abstract: Tuberculosis (TB) remains the deadliest infectious disease1, and the widely used Bacillus Calmette–Guerin (BCG) vaccine fails to curb the epidemic. An improved vaccination strategy could provide a cost-effective intervention to break the transmission cycle and prevent antimicrobial resistance2,3. Limited knowledge of the host responses critically involved in protective immunity hampers the development of improved TB vaccination regimens. Therefore, assessment of new strategies in preclinical models to select the best candidate vaccines before clinical vaccine testing remains indispensable. We have previously established in rhesus macaques (Macaca mulatta) that pulmonary mucosal BCG delivery reduces TB disease where standard intradermal injection fails4,5. Here, we show that pulmonary BCG prevents infection by using a repeated limiting-dose Mycobacterium tuberculosis challenge model and identify polyfunctional T-helper type 17 (TH17) cells, interleukin-10 and immunoglobulin A as correlates of local protective immunity. These findings warrant further research into mucosal immunization strategies and their translation to clinical application to more effectively prevent the spread of TB. Delivery of the Bacillus Calmette–Guerin vaccine into the lungs but not the skin of rhesus macaques protects animals from infection with Mycobacterium tuberculosis, suggesting that immune responses elicited locally may be required for vaccine efficacy.
177 citations
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28,685 citations
01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
4,409 citations
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Rockefeller University1, University of Basel2, Memorial Sloan Kettering Cancer Center3, Swiss Institute of Bioinformatics4, Sapienza University of Rome5, German Cancer Research Center6, Ludwig Maximilian University of Munich7, University of Freiburg8, Miltenyi Biotec9, J. Craig Venter Institute10, Columbia University11, University of Naples Federico II12, University of Düsseldorf13, University of Bonn14, Semmelweis University15, Yeshiva University16, National Institutes of Health17, Cornell University18
TL;DR: A relatively small set of miRNAs, many of which are ubiquitously expressed, account for most of the differences in miRNA profiles between cell lineages and tissues.
3,687 citations
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TL;DR: Current studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains, and microglial cells are considered the most susceptible sensors of brain pathology.
Abstract: Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.
2,998 citations
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TL;DR: An astounding potential exists for next-generation DNA sequencing technologies to bring enormous change in genetic and biological research and to enhance the authors' fundamental biological knowledge.
Abstract: Recent scientific discoveries that resulted from the application of nextgeneration DNA sequencing technologies highlight the striking impact of these massively parallel platforms on genetics. These new methods have expanded previously focused readouts from a variety of DNA preparation protocols to a genome-wide scale and have fine-tuned their resolution to single base precision. The sequencing of RNA also has transitioned and now includes full-length cDNA analyses, serial analysis of gene expression (SAGE)-based methods, and noncoding RNA discovery. Next-generation sequencing has also enabled novel applications such as the sequencing of ancient DNA samples, and has substantially widened the scope of metagenomic analysis of environmentally derived samples. Taken together, an astounding potential exists for these technologies to bring enormous change in genetic and biological research and to enhance our fundamental biological knowledge.
2,354 citations