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Do echinoderm genomes measure up?

ABSTRACT: Echinoderm genome sequences are a corpus of useful information about a clade of animals that serve as research models in fields ranging from marine ecology to cell and developmental biology. Genomic information from echinoids has contributed to insights into the gene interactions that drive the developmental process at the molecular level. Such insights often rely heavily on genomic information and the kinds of questions that can be asked thus depend on the quality of the sequence information. Here we describe the history of echinoderm genomic sequence assembly and present details about the quality of the data obtained. All of the sequence information discussed here is posted on the echinoderm information web system, Echinobase.org.

SUBMITTER: Cameron RA

PROVIDER: S-EPMC4489978 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Do echinoderm genomes measure up?

Cameron R Andrew RA Kudtarkar Parul P Gordon Susan M SM Worley Kim C KC Gibbs Richard A RA

Marine genomics 20150217

Echinoderm genome sequences are a corpus of useful information about a clade of animals that serve as research models in fields ranging from marine ecology to cell and developmental biology. Genomic information from echinoids has contributed to insights into the gene interactions that drive the developmental process at the molecular level. Such insights often rely heavily on genomic information and the kinds of questions that can be asked thus depend on the quality of the sequence information. H ...[more]

PMID: 25701080

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Project description:BackgroundRecent genomic information has revealed that neuroglobin and cytoglobin are the two principal lineages of vertebrate hemoglobins, with the latter encompassing the familiar myoglobin and α-globin/β-globin tetramer hemoglobin, and several minor groups. In contrast, very little is known about hemoglobins in echinoderms, a phylum of exclusively marine organisms closely related to vertebrates, beyond the presence of coelomic hemoglobins in sea cucumbers and brittle stars. We identified about 50 hemoglobins in sea urchin, starfish and sea cucumber genomes and transcriptomes, and used Bayesian inference to carry out a molecular phylogenetic analysis of their relationship to vertebrate sequences, specifically, to assess the hypothesis that the neuroglobin and cytoglobin lineages are also present in echinoderms.ResultsThe genome of the sea urchin Strongylocentrotus purpuratus encodes several hemoglobins, including a unique chimeric 14-domain globin, 2 androglobin isoforms and a unique single androglobin domain protein. Other strongylocentrotid genomes appear to have similar repertoires of globin genes. We carried out molecular phylogenetic analyses of 52 hemoglobins identified in sea urchin, brittle star and sea cucumber genomes and transcriptomes, using different multiple sequence alignment methods coupled with Bayesian and maximum likelihood approaches. The results demonstrate that there are two major globin lineages in echinoderms, which are related to the vertebrate neuroglobin and cytoglobin lineages. Furthermore, the brittle star and sea cucumber coelomic hemoglobins appear to have evolved independently from the cytoglobin lineage, similar to the evolution of erythroid oxygen binding globins in cyclostomes and vertebrates.ConclusionThe presence of echinoderm globins related to the vertebrate neuroglobin and cytoglobin lineages suggests that the split between neuroglobins and cytoglobins occurred in the deuterostome ancestor shared by echinoderms and vertebrates.

Project description:ImportanceAtopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population.ObjectiveTo assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents.Design, setting, and participantsPrespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021.InterventionsPatients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up).Main outcomes and measuresSafety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points).ResultsA total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate.Conclusions and relevanceIn this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile.Trial registrationClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up).

Project description:ImportancePrimary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown.ObjectiveTo evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis.Design, setting, and participantsMeasure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults and adolescents with moderate to severe atopic dermatitis at 151 and 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2).InterventionsPatients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner.Main outcomes and measuresSafety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed.ResultsMeasure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals.Conclusions and relevanceIn this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks.Trial registrationClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2).

Dataset Information

Do echinoderm genomes measure up?

Publications

Do echinoderm genomes measure up?

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