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Article ; Online: Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.

Mahmoud, Ismail Sami / Jarrar, Yazun Bashir / Febrimarsa

2023 Volume 23, Issue 6, Page(s) 2909–2923

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current pandemic coronavirus disease 2019 (COVID-19). Dysregulated and excessive production of cytokines and chemokines, known as cytokine storm, is frequently seen in ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current pandemic coronavirus disease 2019 (COVID-19). Dysregulated and excessive production of cytokines and chemokines, known as cytokine storm, is frequently seen in patients with severe COVID-19 disease and it can provoke a severe systematic inflammation in the patients. The IL-1R/TLRs/IRAKs signaling network is a key pathway in immune cells that plays a central role in regulating innate immunity and inflammatory responses via stimulating the expression and production of various proinflammatory molecules including cytokines. Modulation of IRAKs activity has been proposed to be a promising strategy in the treatment of inflammatory disorders. In this review, we highlight the biochemical properties of IRAKs and their role in regulating inflammatory molecular signaling pathways and discuss the potential targeting of IRAKs to suppress the SARS-CoV-2-induced cytokine storm in COVID-19 patients.
MeSH term(s)	Humans ; COVID-19 ; Cytokine Release Syndrome/drug therapy ; Cytokines ; Immunity, Innate ; SARS-CoV-2
Chemical Substances	Cytokines
Language	English
Publishing date	2023-04-15
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-023-01064-7
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Article ; Online: Gene Manipulation in Hydractinia.

Chrysostomou, Eleni / Febrimarsa / DuBuc, Timothy / Frank, Uri

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2450, Page(s) 419–436

Abstract: The ability to regenerate lost body parts is irregularly distributed among animals, with substantial differences in regenerative potential between and within metazoan phyla. It is widely believed that regenerative animal clades inherited some aspects of ... ...

Abstract	The ability to regenerate lost body parts is irregularly distributed among animals, with substantial differences in regenerative potential between and within metazoan phyla. It is widely believed that regenerative animal clades inherited some aspects of their capacity to regenerate from their common ancestors but have also evolved new mechanisms that are not shared with other regenerative animals. Therefore, to gain a broad understanding of animal regenerative mechanisms and evolution, a broad sampling approach is necessary. Unfortunately, only few regenerative animals have been established as laboratory models with protocols for functional gene studies. Here, we describe the methods to establish transgenic individuals of the marine cnidarian Hydractinia. We also provide methods for transient gene expression manipulation without modifying the genome of the animals.
MeSH term(s)	Animals ; Cnidaria/physiology ; Regeneration
Language	English
Publishing date	2022-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2172-1_22
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Article ; Online: Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration.

Salinas-Saavedra, Miguel / Febrimarsa / Krasovec, Gabriel / Horkan, Helen R / Baxevanis, Andreas D / Frank, Uri

Cell reports

2023 Volume 42, Issue 7, Page(s) 112687

Abstract: Cell fate stability is essential to maintaining "law and order" in complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern ... ...

Abstract	Cell fate stability is essential to maintaining "law and order" in complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern animals being rather simple and regenerative or complex and non-regenerative. The mechanisms mediating cellular plasticity and allowing for regeneration remain unknown. We show that signals emitted by senescent cells can destabilize the differentiated state of neighboring somatic cells, reprogramming them into stem cells that are capable of driving whole-body regeneration in the cnidarian Hydractinia symbiolongicarpus. Pharmacological or genetic inhibition of senescence prevents reprogramming and regeneration. Conversely, induction of transient ectopic senescence in a regenerative context results in supernumerary stem cells and faster regeneration. We propose that senescence signaling is an ancient mechanism mediating cellular plasticity. Understanding the senescence environment that promotes cellular reprogramming could provide an avenue to enhance regeneration.
MeSH term(s)	Animals ; Cnidaria ; Cellular Reprogramming ; Cellular Senescence/genetics ; Signal Transduction ; Stem Cells
Language	English
Publishing date	2023-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Intramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112687
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Article ; Online: Chromosome-level genome assembly of Hydractinia symbiolongicarpus.

Kon-Nanjo, Koto / Kon, Tetsuo / Horkan, Helen R / Febrimarsa / Steele, Robert E / Cartwright, Paulyn / Frank, Uri / Simakov, Oleg

G3 (Bethesda, Md.)

2023

Abstract: Hydractinia symbiolongicarpus is a pioneering model organism for stem cell biology, being one of only a few animals with adult pluripotent stem cells (known as i-cells). However, the unavailability of a chromosome-level genome assembly has hindered a ... ...

Abstract	Hydractinia symbiolongicarpus is a pioneering model organism for stem cell biology, being one of only a few animals with adult pluripotent stem cells (known as i-cells). However, the unavailability of a chromosome-level genome assembly has hindered a comprehensive understanding of global gene regulatory mechanisms underlying the function and evolution of i-cells. Here, we report the first chromosome-level genome assembly of H. symbiolongicarpus (HSymV2.0) using PacBio HiFi long-read sequencing and Hi-C scaffolding. The final assembly is 483 Mb in total length with 15 chromosomes representing 99.8% of the assembly. Repetitive sequences were found to account for 296 Mb (61%) of the total genome; we provide evidence for at least two periods of repeat expansion in the past. A total of 25,825 protein-coding genes were predicted in this assembly, which include 93.1% of the metazoan Benchmarking Universal Single-Copy Orthologs (BUSCO) gene set. 92.8% (23,971 genes) of the predicted proteins were functionally annotated. The H. symbiolongicarpus genome showed a high degree of macrosynteny conservation with the Hydra vulgaris genome. This chromosome-level genome assembly of H. symbiolongicarpus will be an invaluable resource for the research community that enhances broad biological studies on this unique model organism.
Language	English
Publishing date	2023-05-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkad107
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Article ; Online: Randomly incorporated genomic N6-methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian.

Febrimarsa / Gornik, Sebastian G / Barreira, Sofia N / Salinas-Saavedra, Miguel / Schnitzler, Christine E / Baxevanis, Andreas D / Frank, Uri

The EMBO journal

2023 Volume 42, Issue 15, Page(s) e112934

Abstract: N6-methyldeoxyadenosine (6mA) is a chemical alteration of DNA, observed across all realms of life. Although the functions of 6mA are well understood in bacteria and protists, its roles in animal genomes have been controversial. We show that 6mA randomly ... ...

Abstract	N6-methyldeoxyadenosine (6mA) is a chemical alteration of DNA, observed across all realms of life. Although the functions of 6mA are well understood in bacteria and protists, its roles in animal genomes have been controversial. We show that 6mA randomly accumulates in early embryos of the cnidarian Hydractinia symbiolongicarpus, with a peak at the 16-cell stage followed by clearance to background levels two cell cycles later, at the 64-cell stage-the embryonic stage at which zygotic genome activation occurs in this animal. Knocking down Alkbh1, a putative initiator of animal 6mA clearance, resulted in higher levels of 6mA at the 64-cell stage and a delay in the initiation of zygotic transcription. Our data are consistent with 6mA originating from recycled nucleotides of degraded m6A-marked maternal RNA postfertilization. Therefore, while 6mA does not function as an epigenetic mark in Hydractinia, its random incorporation into the early embryonic genome inhibits transcription. In turn, Alkbh1 functions as a genomic 6mA "cleaner," facilitating timely zygotic genome activation. Given the random nature of genomic 6mA accumulation and its ability to interfere with gene expression, defects in 6mA clearance may represent a hitherto unknown cause of various pathologies.
MeSH term(s)	Animals ; Cnidaria ; Genomics ; Kinetics ; Epigenomics ; Cognition
Language	English
Publishing date	2023-07-04
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.15252/embj.2022112934
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Zs.A 1808: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Hydrozoan sperm-specific SPKK motif-containing histone H2B variants stabilise chromatin with limited compaction.

Török, Anna / Browne, Martin J G / Vilar, Jordina C / Patwal, Indu / DuBuc, Timothy Q / Febrimarsa / Atcheson, Erwan / Frank, Uri / Gornik, Sebastian G / Flaus, Andrew

Development (Cambridge, England)

2023 Volume 150, Issue 1

Abstract: Many animals achieve sperm chromatin compaction and stabilisation by replacing canonical histones with sperm nuclear basic proteins (SNBPs) such as protamines during spermatogenesis. Hydrozoan cnidarians and echinoid sea urchins lack protamines and have ... ...

Abstract	Many animals achieve sperm chromatin compaction and stabilisation by replacing canonical histones with sperm nuclear basic proteins (SNBPs) such as protamines during spermatogenesis. Hydrozoan cnidarians and echinoid sea urchins lack protamines and have evolved a distinctive family of sperm-specific histone H2Bs (spH2Bs) with extended N termini rich in SPK(K/R) motifs. Echinoid sperm packaging is regulated by spH2Bs. Their sperm is negatively buoyant and fertilises on the sea floor. Hydroid cnidarians undertake broadcast spawning but their sperm properties are poorly characterised. We show that Hydractinia echinata and H. symbiolongicarpus sperm chromatin possesses higher stability than somatic chromatin, with reduced accessibility to transposase Tn5 integration and to endonucleases in vitro. In contrast, nuclear dimensions are only moderately reduced in mature Hydractinia sperm. Ectopic expression of spH2B in the background of H2B.1 knockdown results in downregulation of global transcription and cell cycle arrest in embryos, without altering their nuclear density. Taken together, SPKK-containing spH2B variants act to stabilise chromatin and silence transcription in Hydractinia sperm with only limited chromatin compaction. We suggest that spH2Bs could contribute to sperm buoyancy as a reproductive adaptation.
MeSH term(s)	Animals ; Male ; Histones/metabolism ; Chromatin/metabolism ; Hydrozoa/genetics ; Semen/metabolism ; Spermatozoa/metabolism ; Protamines/metabolism
Chemical Substances	Histones ; Chromatin ; seryl-prolyl-lysyl-lysine (121106-80-7) ; Protamines
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.201058
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Zs.MG 91: Show issues

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Article ; Online: The genome of the colonial hydroid

Schnitzler, Christine E / Chang, E Sally / Waletich, Justin / Quiroga-Artigas, Gonzalo / Wong, Wai Yee / Nguyen, Anh-Dao / Barreira, Sofia N / Doonan, Liam B / Gonzalez, Paul / Koren, Sergey / Gahan, James M / Sanders, Steven M / Bradshaw, Brian / DuBuc, Timothy Q / Febrimarsa / de Jong, Danielle / Nawrocki, Eric P / Larson, Alexandra / Klasfeld, Samantha /

Gornik, Sebastian G / Moreland, R Travis / Wolfsberg, Tyra G / Phillippy, Adam M / Mullikin, James C / Simakov, Oleg / Cartwright, Paulyn / Nicotra, Matthew / Frank, Uri / Baxevanis, Andreas D

Genome research

2024 Volume 34, Issue 3, Page(s) 498–513

Abstract: ... ...

Abstract	Hydractinia
MeSH term(s)	Animals ; Hydrozoa/genetics ; Genome ; Evolution, Molecular ; Transcriptome ; Stem Cells/metabolism ; Male ; Phylogeny ; Single-Cell Analysis/methods
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.278382.123
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Zs.A 3729: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Transcription factor AP2 controls cnidarian germ cell induction.

DuBuc, Timothy Q / Schnitzler, Christine E / Chrysostomou, Eleni / McMahon, Emma T / Febrimarsa / Gahan, James M / Buggie, Tara / Gornik, Sebastian G / Hanley, Shirley / Barreira, Sofia N / Gonzalez, Paul / Baxevanis, Andreas D / Frank, Uri

Science (New York, N.Y.)

2020 Volume 367, Issue 6479, Page(s) 757–762

Abstract: Clonal animals do not sequester a germ line during embryogenesis. Instead, they have adult stem cells that contribute to somatic tissues or gametes. How germ fate is induced in these animals, and whether this process is related to bilaterian embryonic ... ...

Abstract	Clonal animals do not sequester a germ line during embryogenesis. Instead, they have adult stem cells that contribute to somatic tissues or gametes. How germ fate is induced in these animals, and whether this process is related to bilaterian embryonic germline induction, is unknown. We show that transcription factor AP2 (Tfap2), a regulator of mammalian germ lines, acts to commit adult stem cells, known as i-cells, to the germ cell fate in the clonal cnidarian
MeSH term(s)	Adult Stem Cells/cytology ; Adult Stem Cells/metabolism ; Animals ; Female ; Gametogenesis/genetics ; Gametogenesis/physiology ; Gene Expression Regulation, Developmental ; Germ Cells/cytology ; Gonads/cytology ; Gonads/embryology ; Hydrozoa/cytology ; Hydrozoa/embryology ; Hydrozoa/genetics ; Male ; Transcription Factor AP-2/genetics ; Transcription Factor AP-2/physiology
Chemical Substances	Transcription Factor AP-2
Language	English
Publishing date	2020-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aay6782
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Article: The genome of the colonial hydroid

Schnitzler, Christine E / Chang, E Sally / Waletich, Justin / Quiroga-Artigas, Gonzalo / Wong, Wai Yee / Nguyen, Anh-Dao / Barreira, Sofia N / Doonan, Liam / Gonzalez, Paul / Koren, Sergey / Gahan, James M / Sanders, Steven M / Bradshaw, Brian / DuBuc, Timothy Q / Febrimarsa / de Jong, Danielle / Nawrocki, Eric P / Larson, Alexandra / Klasfeld, Samantha /

Gornik, Sebastian G / Moreland, R Travis / Wolfsberg, Tyra G / Phillippy, Adam M / Mullikin, James C / Simakov, Oleg / Cartwright, Paulyn / Nicotra, Matthew / Frank, Uri / Baxevanis, Andreas D

bioRxiv : the preprint server for biology

2023

Abstract: ... ...

Abstract	Hydractinia
Language	English
Publishing date	2023-08-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.25.554815
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Article ; Online: Endosymbiosis undone by stepwise elimination of the plastid in a parasitic dinoflagellate.

Gornik, Sebastian G / Febrimarsa / Cassin, Andrew M / MacRae, James I / Ramaprasad, Abhinay / Rchiad, Zineb / McConville, Malcolm J / Bacic, Antony / McFadden, Geoffrey I / Pain, Arnab / Waller, Ross F

Proceedings of the National Academy of Sciences of the United States of America

2015 Volume 112, Issue 18, Page(s) 5767–5772

Abstract: Organelle gain through endosymbiosis has been integral to the origin and diversification of eukaryotes, and, once gained, plastids and mitochondria seem seldom lost. Indeed, discovery of nonphotosynthetic plastids in many eukaryotes--notably, the ... ...

Abstract	Organelle gain through endosymbiosis has been integral to the origin and diversification of eukaryotes, and, once gained, plastids and mitochondria seem seldom lost. Indeed, discovery of nonphotosynthetic plastids in many eukaryotes--notably, the apicoplast in apicomplexan parasites such as the malaria pathogen Plasmodium--highlights the essential metabolic functions performed by plastids beyond photosynthesis. Once a cell becomes reliant on these ancillary functions, organelle dependence is apparently difficult to overcome. Previous examples of endosymbiotic organelle loss (either mitochondria or plastids), which have been invoked to explain the origin of eukaryotic diversity, have subsequently been recognized as organelle reduction to cryptic forms, such as mitosomes and apicoplasts. Integration of these ancient symbionts with their hosts has been too well developed to reverse. Here, we provide evidence that the dinoflagellate Hematodinium sp., a marine parasite of crustaceans, represents a rare case of endosymbiotic organelle loss by the elimination of the plastid. Extensive RNA and genomic sequencing data provide no evidence for a plastid organelle, but, rather, reveal a metabolic decoupling from known plastid functions that typically impede organelle loss. This independence has been achieved through retention of ancestral anabolic pathways, enzyme relocation from the plastid to the cytosol, and metabolic scavenging from the parasite's host. Hematodinium sp. thus represents a further dimension of endosymbiosis--life after the organelle.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Amino Acid Oxidoreductases/metabolism ; Animals ; Cell Nucleus/metabolism ; Crustacea ; Cytosol/metabolism ; Dinoflagellida/genetics ; Dinoflagellida/physiology ; Fatty Acid Synthases/metabolism ; Fatty Acids/metabolism ; Mitochondria/metabolism ; Molecular Sequence Data ; Parasites ; Photosynthesis ; Phylogeny ; Plasmodium ; Plastids/genetics ; RNA/metabolism ; Symbiosis/genetics ; Transcriptome
Chemical Substances	Fatty Acids ; RNA (63231-63-0) ; Adenosine Triphosphate (8L70Q75FXE) ; Amino Acid Oxidoreductases (EC 1.4.-) ; diaminopimelate dehydrogenase (EC 1.4.1.16) ; Fatty Acid Synthases (EC 2.3.1.85)
Language	English
Publishing date	2015-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1423400112
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