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Article ; Online: To be or not to be: The active inference of suicide.

Krupnik, Valery / Danilova, Nadia

2024 Volume 157, Page(s) 105531

Abstract: Suicide presents an apparent paradox as a behavior whose motivation is not obvious since its outcome is non-existence and cannot be experienced. To address this paradox, we propose to frame suicide in the integrated theory of stress and active inference. ...

Abstract	Suicide presents an apparent paradox as a behavior whose motivation is not obvious since its outcome is non-existence and cannot be experienced. To address this paradox, we propose to frame suicide in the integrated theory of stress and active inference. We present an active inference-based cognitive model of suicide as a type of stress response hanging in cognitive balance between predicting self-preservation and self-destruction. In it, self-efficacy emerges as a meta-cognitive regulator that can bias the model toward either survival or suicide. The model suggests conditions under which cognitive homeostasis can override physiological homeostasis in motivating self-destruction. We also present a model proto-suicidal behavior, programmed cell death (apoptosis), in active inference terms to illustrate how an active inference model of self-destruction can be embodied in molecular mechanisms and to offer a hypothesis on another puzzle of suicide: why only humans among brain-endowed animals are known to practice it.
MeSH term(s)	Animals ; Humans ; Suicide/psychology ; Self-Injurious Behavior/psychology ; Suicidal Ideation ; Brain/physiology ; Motivation
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2023.105531
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Article: The evolution of adaptive immunity.

Danilova, Nadia

Advances in experimental medicine and biology

2012 Volume 738, Page(s) 218–235

Abstract: The concept of adaptive immunity suggests de novo generation in each individual of extremely large repertoires of diversified receptors and selective expansion of receptors that match the antigen/pathogen. Accordingly, adaptive immune system is also ... ...

Abstract	The concept of adaptive immunity suggests de novo generation in each individual of extremely large repertoires of diversified receptors and selective expansion of receptors that match the antigen/pathogen. Accordingly, adaptive immune system is also called "anticipatory". It allows each individual to have a unique repertoire of immune receptors corresponding to its life history. The memory of an antigen gets encoded in the clonal composition of the organism's immune cells instead of being encoded in the genome. Consequently, the immune response to repeated encounter with the same antigen becomes stronger, a phenomenon called immunological memory. Elements of adaptive immunity are found at all taxonomical levels, whereas in vertebrates, adaptive mechanisms have become the cornerstone of the immune system. In jaw vertebrates, adaptive immune receptors of T and B lymphoid cells belong to immunoglobulin superfamily and are created by rearrangement of gene segments. In jawless vertebrates lamprey and hagfish, recombination of leucine-rich repeat modules is used to form variable lymphocyte receptors. Striking functional similarity of the cellular and humoral branches of these systems suggests similar driving forces underlying their development.
MeSH term(s)	Adaptive Immunity/physiology ; Animals ; Antigens/genetics ; Antigens/immunology ; B-Lymphocytes/immunology ; Evolution, Molecular ; Host-Pathogen Interactions/physiology ; Humans ; Immunologic Memory/physiology ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/immunology ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/immunology
Chemical Substances	Antigens ; Receptors, Antigen, B-Cell ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2012
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-1-4614-1680-7_13
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Ribosomopathies: how a common root can cause a tree of pathologies.

Danilova, Nadia / Gazda, Hanna T

Disease models & mechanisms

2015 Volume 8, Issue 9, Page(s) 1013–1026

Abstract: Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple ... ...

Abstract	Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple other factors are necessary for the processing of pre-rRNA, the assembly of ribosomal subunits, their export to the cytoplasm and for the final assembly of subunits into a ribosome. Haploinsufficiency of certain RPs causes DBA, whereas mutations in other factors cause various other ribosomopathies. Despite the general nature of their underlying defects, the clinical manifestations of ribosomopathies differ. In DBA, for example, red blood cell pathology is especially evident. In addition, individuals with DBA often have malformations of limbs, the face and various organs, and also have an increased risk of cancer. Common features shared among human DBA and animal models have emerged, such as small body size, eye defects, duplication or overgrowth of ectoderm-derived structures, and hematopoietic defects. Phenotypes of ribosomopathies are mediated both by p53-dependent and -independent pathways. The current challenge is to identify differences in response to ribosomal stress that lead to specific tissue defects in various ribosomopathies. Here, we review recent findings in this field, with a particular focus on animal models, and discuss how, in some cases, the different phenotypes of ribosomopathies might arise from differences in the spatiotemporal expression of the affected genes.
MeSH term(s)	Anemia, Diamond-Blackfan/blood ; Anemia, Diamond-Blackfan/genetics ; Anemia, Diamond-Blackfan/physiopathology ; Animals ; Cell Cycle ; Cell Proliferation ; Disease Models, Animal ; Erythrocytes/pathology ; Erythropoiesis ; Hematopoiesis ; Humans ; Immunity, Innate ; Mutation ; Neoplasms/metabolism ; Phenotype ; RNA, Ribosomal/analysis ; Ribosomal Proteins/genetics ; Ribosomes/pathology ; Ribosomes/ultrastructure ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	RNA, Ribosomal ; Ribosomal Proteins ; Tumor Suppressor Protein p53
Language	English
Publishing date	2015-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	1754-8411
ISSN (online)	1754-8411
DOI	10.1242/dmm.020529
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Article: The evolution of immune mechanisms.

Danilova, Nadia

Journal of experimental zoology. Part B, Molecular and developmental evolution

2006 Volume 306, Issue 6, Page(s) 496–520

Abstract: From early on in evolution, organisms have had to protect themselves from pathogens. Mechanisms for discriminating "self" from "non-self" evolved to accomplish this task, launching a long history of host-pathogen co-evolution. Evolution of mechanisms of ... ...

Abstract	From early on in evolution, organisms have had to protect themselves from pathogens. Mechanisms for discriminating "self" from "non-self" evolved to accomplish this task, launching a long history of host-pathogen co-evolution. Evolution of mechanisms of immune defense has resulted in a variety of strategies. Even unicellular organisms have rich arsenals of mechanisms for protection, such as restriction endonucleases, antimicrobial peptides, and RNA interference. In multicellular organisms, specialized immune cells have evolved, capable of recognition, phagocytosis, and killing of foreign cells as well as removing their own cells changed by damage, senescence, infection, or cancer. Additional humoral factors, such as the complement cascade, have developed that co-operate with cellular immunity in fighting infection and maintaining homeostasis. Defensive mechanisms based on germline-encoded receptors constitute a system known as innate immunity. In jaw vertebrates, this system is supplemented with a second system, adaptive immunity, which in contrast to innate immunity is based on diversification of immune receptors and on immunological memory in each individual.Usually, each newly evolved defense mechanism did not replace the previous one, but supplemented it, resulting in a layered structure of the immune system. The immune system is not one system but rather a sophisticated network of various defensive mechanisms operating on different levels, ranging from mechanisms common for every cell in the body to specialized immune cells and responses at the level of the whole organism. Adaptive changes in pathogens have shaped the evolution of the immune system at all levels.
MeSH term(s)	Adaptation, Biological/immunology ; Antimicrobial Cationic Peptides/immunology ; Apoptosis/immunology ; Biological Evolution ; Complement System Proteins/immunology ; Immunity/genetics ; Immunity/immunology ; Phagocytosis/immunology ; RNA Interference ; Receptor Cross-Talk/immunology
Chemical Substances	Antimicrobial Cationic Peptides ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2006-11-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2113204-5
ISSN	1552-5015 ; 1552-5007
ISSN (online)	1552-5015
ISSN	1552-5007
DOI	10.1002/jez.b.21102
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Article ; Online: Ribosomopathies

Nadia Danilova / Hanna T. Gazda

Disease Models & Mechanisms, Vol 8, Iss 9, Pp 1013-

how a common root can cause a tree of pathologies

2015 Volume 1026

Abstract	Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple other factors are necessary for the processing of pre-rRNA, the assembly of ribosomal subunits, their export to the cytoplasm and for the final assembly of subunits into a ribosome. Haploinsufficiency of certain RPs causes DBA, whereas mutations in other factors cause various other ribosomopathies. Despite the general nature of their underlying defects, the clinical manifestations of ribosomopathies differ. In DBA, for example, red blood cell pathology is especially evident. In addition, individuals with DBA often have malformations of limbs, the face and various organs, and also have an increased risk of cancer. Common features shared among human DBA and animal models have emerged, such as small body size, eye defects, duplication or overgrowth of ectoderm-derived structures, and hematopoietic defects. Phenotypes of ribosomopathies are mediated both by p53-dependent and -independent pathways. The current challenge is to identify differences in response to ribosomal stress that lead to specific tissue defects in various ribosomopathies. Here, we review recent findings in this field, with a particular focus on animal models, and discuss how, in some cases, the different phenotypes of ribosomopathies might arise from differences in the spatiotemporal expression of the affected genes.
Keywords	Ribosome biogenesis ; Ribosomal protein ; Ribosomopathy ; Diamond-Blackfan anemia ; p53 ; ΔNp63 ; Medicine ; R ; Pathology ; RB1-214
Subject code	571 ; 610
Language	English
Publishing date	2015-09-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Analysis of recombination signal sequences in zebrafish.

Danilova, Nadia

Molecular immunology

2005 Volume 42, Issue 10, Page(s) 1243–1249

Abstract: Recombination signal sequences (RSS) from immunoglobulin and TCRalpha genes of zebrafish were analyzed in comparison with RSS from human and species-specific features were revealed. In contrast to human RSS, in zebrafish RSS from both V(H) and TCRalpha ... ...

Abstract	Recombination signal sequences (RSS) from immunoglobulin and TCRalpha genes of zebrafish were analyzed in comparison with RSS from human and species-specific features were revealed. In contrast to human RSS, in zebrafish RSS from both V(H) and TCRalpha genes the last nonamer position is not conserved. On the contrary, the fourth nonamer position, which is not conserved in human or mouse is conserved in zebrafish. The 12 bp spacers from human and zebrafish RSS contain 9 bp motif resembling nonamer sequence. Spacers in zebrafish 23 bp RSS from both immunoglobulins and TCRalpha contain 7 bp motif also resembling nonamer sequence while corresponding human sequences do not contain analogous motif. RSS are recognized by RAG1 protein, which also has specific features in teleost suggesting co-evolution of RAG1 with corresponding RSS.
MeSH term(s)	Amino Acid Sequence ; Animals ; Base Sequence ; Conserved Sequence ; DNA, Intergenic/chemistry ; DNA, Intergenic/genetics ; Evolution, Molecular ; Genes, Immunoglobulin ; Homeodomain Proteins/chemistry ; Homeodomain Proteins/genetics ; Humans ; Immunoglobulin Variable Region/genetics ; Molecular Sequence Data ; Receptors, Antigen, T-Cell/genetics ; Recombination, Genetic/immunology ; Sequence Homology, Amino Acid ; Species Specificity ; Zebrafish/genetics
Chemical Substances	DNA, Intergenic ; Homeodomain Proteins ; Immunoglobulin Variable Region ; Receptors, Antigen, T-Cell ; RAG-1 protein (128559-51-3)
Language	English
Publishing date	2005-06
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2004.11.022
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Article ; Online: Innate immune system activation in zebrafish and cellular models of Diamond Blackfan Anemia.

Danilova, Nadia / Wilkes, Mark / Bibikova, Elena / Youn, Min-Young / Sakamoto, Kathleen M / Lin, Shuo

Scientific reports

2018 Volume 8, Issue 1, Page(s) 5165

Abstract: Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA) associated with anemia, congenital defects, and cancer. While p53 activation is responsible for many features of DBA, the role of immune system is less defined. The Innate ... ...

Abstract	Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA) associated with anemia, congenital defects, and cancer. While p53 activation is responsible for many features of DBA, the role of immune system is less defined. The Innate immune system can be activated by endogenous nucleic acids from non-processed pre-rRNAs, DNA damage, and apoptosis that occurs in DBA. Recognition by toll like receptors (TLRs) and Mda5-like sensors induces interferons (IFNs) and inflammation. Dying cells can also activate complement system. Therefore we analyzed the status of these pathways in RP-deficient zebrafish and found upregulation of interferon, inflammatory cytokines and mediators, and complement. We also found upregulation of receptors signaling to IFNs including Mda5, Tlr3, and Tlr9. TGFb family member activin was also upregulated in RP-deficient zebrafish and in RPS19-deficient human cells, which include a lymphoid cell line from a DBA patient, and fetal liver cells and K562 cells transduced with RPS19 shRNA. Treatment of RP-deficient zebrafish with a TLR3 inhibitor decreased IFNs activation, acute phase response, and apoptosis and improved their hematopoiesis and morphology. Inhibitors of complement and activin also had beneficial effects. Our studies suggest that innate immune system contributes to the phenotype of RPS19-deficient zebrafish and human cells.
MeSH term(s)	Activin Receptors/antagonists & inhibitors ; Activins/metabolism ; Anemia, Diamond-Blackfan/immunology ; Anemia, Diamond-Blackfan/metabolism ; Animals ; Arginine/analogs & derivatives ; Arginine/pharmacology ; Benzamides/pharmacology ; Benzhydryl Compounds/pharmacology ; Complement C3a/antagonists & inhibitors ; Complement C3a/metabolism ; Dioxoles/pharmacology ; Disease Models, Animal ; Humans ; Immunity, Innate/physiology ; Interferons/metabolism ; K562 Cells ; RNA, Small Interfering/metabolism ; Receptor, Transforming Growth Factor-beta Type I/antagonists & inhibitors ; Ribosomal Proteins/metabolism ; Toll-Like Receptor 3/antagonists & inhibitors ; Toll-Like Receptor 3/metabolism ; Transforming Growth Factor beta/metabolism ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation ; Zebrafish/embryology ; Zebrafish/immunology ; Zebrafish/metabolism ; Zebrafish Proteins/metabolism
Chemical Substances	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide ; Benzamides ; Benzhydryl Compounds ; Dioxoles ; RNA, Small Interfering ; RPS19 protein, zebrafish ; Ribosomal Proteins ; SB 290157 ; TLR3 protein, human ; Toll-Like Receptor 3 ; Transforming Growth Factor beta ; Tumor Suppressor Protein p53 ; Zebrafish Proteins ; ribosomal protein S19 ; Activins (104625-48-1) ; Complement C3a (80295-42-7) ; Interferons (9008-11-1) ; Arginine (94ZLA3W45F) ; Activin Receptors (EC 2.7.11.30) ; Receptor, Transforming Growth Factor-beta Type I (EC 2.7.11.30)
Language	English
Publishing date	2018-03-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-23561-6
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Article ; Online: Innate immune system activation in zebrafish and cellular models of Diamond Blackfan Anemia

Nadia Danilova / Mark Wilkes / Elena Bibikova / Min-Young Youn / Kathleen M. Sakamoto / Shuo Lin

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 11

Abstract: Abstract Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA) associated with anemia, congenital defects, and cancer. While p53 activation is responsible for many features of DBA, the role of immune system is less defined. The ... ...

Abstract	Abstract Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA) associated with anemia, congenital defects, and cancer. While p53 activation is responsible for many features of DBA, the role of immune system is less defined. The Innate immune system can be activated by endogenous nucleic acids from non-processed pre-rRNAs, DNA damage, and apoptosis that occurs in DBA. Recognition by toll like receptors (TLRs) and Mda5-like sensors induces interferons (IFNs) and inflammation. Dying cells can also activate complement system. Therefore we analyzed the status of these pathways in RP-deficient zebrafish and found upregulation of interferon, inflammatory cytokines and mediators, and complement. We also found upregulation of receptors signaling to IFNs including Mda5, Tlr3, and Tlr9. TGFb family member activin was also upregulated in RP-deficient zebrafish and in RPS19-deficient human cells, which include a lymphoid cell line from a DBA patient, and fetal liver cells and K562 cells transduced with RPS19 shRNA. Treatment of RP-deficient zebrafish with a TLR3 inhibitor decreased IFNs activation, acute phase response, and apoptosis and improved their hematopoiesis and morphology. Inhibitors of complement and activin also had beneficial effects. Our studies suggest that innate immune system contributes to the phenotype of RPS19-deficient zebrafish and human cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
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Article ; Online: Going adaptive: the saga of antibodies.

Danilova, Nadia / Amemiya, Chris T

Annals of the New York Academy of Sciences

2009 Volume 1168, Page(s) 130–155

Abstract: Because of their extreme importance to human health, we probably know more about the structure and function of antibodies than practically any other molecule. Despite all the knowledge that has been accrued in the understanding of antibodies, modern ... ...

Abstract	Because of their extreme importance to human health, we probably know more about the structure and function of antibodies than practically any other molecule. Despite all the knowledge that has been accrued in the understanding of antibodies, modern approaches, especially comparative genomics, continue to yield novel findings regarding their underlying biology and evolution. In this review, we describe recent research that led to these revelations, and discuss the broad evolutionary implications of these findings. We have restricted our discussion to three vignettes. Considerable attention has been paid to the recent discovery that the teleost IgH locus is highly similar in organization to the Tcra-Tcrd locus, implicating an evolutionary common ancestor and parallels between the functions of B and T cells during development. Second, we discuss how a new type of antibody, recently discovered in jawless vertebrates, composed not of immunoglobulins but leucine-rich repeats, sheds new light on the overall forces driving evolution of all adaptive antigen receptors. Lastly, we discuss how accumulation of genomic sequences of various human subpopulations leads to better understanding of the directionality of antibody evolution. There is always more to learn from the unfolding saga of antibodies.
MeSH term(s)	Animals ; Antibodies/genetics ; Antibodies/immunology ; Biological Evolution ; Humans ; Immunoglobulins/genetics ; Immunoglobulins/immunology ; Receptors, Antigen/genetics ; Receptors, Antigen/immunology ; Vertebrates/genetics ; Vertebrates/immunology
Chemical Substances	Antibodies ; Immunoglobulins ; Receptors, Antigen
Language	English
Publishing date	2009-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1111/j.1749-6632.2009.04881.x
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Article ; Online: p53 upregulation is a frequent response to deficiency of cell-essential genes.

Danilova, Nadia / Kumagai, Asako / Lin, Jenny

PloS one

2010 Volume 5, Issue 12, Page(s) e15938

Abstract: Background: The role of p53 in the prevention of development of embryos damaged by genotoxic factors is well recognized. However, whether p53 plays an analogous role in preventing birth defects from genetic mutations remains an unanswered question. ... ...

Abstract	Background: The role of p53 in the prevention of development of embryos damaged by genotoxic factors is well recognized. However, whether p53 plays an analogous role in preventing birth defects from genetic mutations remains an unanswered question. Genetic screens for mutations affecting development show that only a fraction of developmentally lethal mutations leads to specific phenotypes while the majority results in similar recurrent phenotypes characterized by neuronal apoptosis and developmental delay. Mutations in cell-essential genes typically fall into this group. The observation that mutations in diverse housekeeping genes lead to a similar phenotype suggests a common mechanism underlying this phenotype. For some mutants, p53 inhibition was shown to attenuate the phenotype. Methodology/principal findings: To find out how common p53 involvement is in this phenotype, we analyzed zebrafish mutants from various categories of cell essential genes. Several thousand zebrafish mutants have been identified; many of them are kept at stock centers and available for the research community. We selected mutants for genes functioning in DNA replication, transcription, telomere maintenance, ribosome biogenesis, splicing, chaperoning, endocytosis, and cellular transport. We found that mutants have similar phenotypes including neural apoptosis, failure to develop structures originated from the neural crest cells, and hematopoietic defects. All mutants share p53 upregulation and similar changes in several p53-dependent and independent molecular pathways. Conclusion/significance: Our results suggest that mutations in housekeeping genes often canalize on the p53-mediated phenotype. p53 prevents the development of embryos with defects in such genes. p53-mediated changes in gene expression may also contribute to many human congenital malformations.
MeSH term(s)	Animals ; Apoptosis ; Gene Expression Regulation, Developmental ; Genes, p53 ; Humans ; In Situ Hybridization ; Models, Animal ; Models, Biological ; Models, Genetic ; Mutation ; Neurons/metabolism ; Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Zebrafish
Chemical Substances	Tumor Suppressor Protein p53
Language	English
Publishing date	2010-12-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0015938
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