Author Correction: The axolotl genome and the evolution of key tissue formation regulators.

In the originally published version of this Article, the sequenced axolotl strain (the homozygous white mutant) was denoted as 'D/D' rather than 'd/d' in Fig. 1a and the accompanying legend, the main text and the Methods section. The original Article has been corrected online.

The axolotl genome and the evolution of key tissue formation regulators.

Salamanders serve as important tetrapod models for developmental, regeneration and evolutionary studies. An extensive molecular toolkit makes the Mexican axolotl (Ambystoma mexicanum) a key representative salamander for molecular investigations. Here we report the sequencing and assembly of the 32-gigabase-pair axolotl genome using an approach that combined long-read sequencing, optical mapping and development of a new genome assembler (MARVEL). We observed a size expansion of introns and intergenic regions, largely attributable to multiplication of long terminal repeat retroelements. We provide evidence that intron size in developmental genes is under constraint and that species-restricted genes may contribute to limb regeneration. The axolotl genome assembly does not contain the essential developmental gene Pax3. However, mutation of the axolotl Pax3 paralogue Pax7 resulted in an axolotl phenotype that was similar to those seen in Pax3-/- and Pax7-/- mutant mice. The axolotl genome provides a rich biological resource for developmental and evolutionary studies.

The giant axolotl genome uncovers the evolution, scaling, and transcriptional control of complex gene loci.

Vertebrates harbor recognizably orthologous gene complements but vary 100-fold in genome size. How chromosomal organization scales with genome expansion is unclear, and how acute changes in gene regulation, as during axolotl limb regeneration, occur in the context of a vast genome has remained a riddle. Here, we describe the chromosome-scale assembly of the giant, 32 Gb axolotl genome. Hi-C contact data revealed the scaling properties of interphase and mitotic chromosome organization. Analysis of the assembly yielded understanding of the evolution of large, syntenic multigene clusters, including the Major Histocompatibility Complex (MHC) and the functional regulatory landscape of the Fibroblast Growth Factor 8 (Axfgf8) region. The axolotl serves as a primary model for studying successful regeneration.

Transcriptional profiling of the CAM plant Agave salmiana reveals conservation of a genetic program for regeneration.

In plants, the best characterized plant regeneration process is de novo organogenesis. This type of regeneration is characterized by the formation of a multicellular structure called callus. Calli are induced via phytohormone treatment of plant sections. The callus formation in plants like Agave species with Crassulacean Acid Metabolism (CAM) is poorly studied. In this study, we induced callus formation from Agave salmiana leaves and describe cell arrangement in this tissue. Moreover, we determined and analyzed the transcriptional program of calli, as well as those of differentiated root and leaf tissues, by using RNA-seq. We were able to reconstruct 170,844 transcripts of which 40,644 have a full Open Reading Frame (ORF). The global profile obtained by Next Generation Sequencing (NGS) reveals that several callus-enriched protein coding transcripts are orthologs of previously reported factors highly expressed in Arabidopsis calli. At least 62 genes were differentially expressed in Agave calli, 50 of which were up-regulated. Several of these are actively involved in the perception of, and response to, auxin and cytokinin. Not only are these the first results for the A. salmiana callus, but they provide novel data from roots and leaves of this Agave species, one of the largest non-tree plants in nature.

Transcriptional landscapes of Axolotl (Ambystoma mexicanum).

The axolotl (Ambystoma mexicanum) is the vertebrate model system with the highest regeneration capacity. Experimental tools established over the past 100 years have been fundamental to start unraveling the cellular and molecular basis of tissue and limb regeneration. In the absence of a reference genome for the Axolotl, transcriptomic analysis become fundamental to understand the genetic basis of regeneration. Here we present one of the most diverse transcriptomic data sets for Axolotl by profiling coding and non-coding RNAs from diverse tissues. We reconstructed a population of 115,906 putative protein coding mRNAs as full ORFs (including isoforms). We also identified 352 conserved miRNAs and 297 novel putative mature miRNAs. Systematic enrichment analysis of gene expression allowed us to identify tissue-specific protein-coding transcripts. We also found putative novel and conserved microRNAs which potentially target mRNAs which are reported as important disease candidates in heart and liver.

Transposon waves at the water-to-land transition.

The major transitions in vertebrate evolution are associated with significant genomic reorganizations. In contrast to the evolutionary processes that occurred at the origin of vertebrates or prior to the radiation of teleost fishes, no whole-genome duplication events occurred during the water-to-land transition, and it remains an open question how did genome dynamics contribute to this prominent evolutionary event. Indeed, the recent sequencing of sarcopterygian and amphibian genomes has revealed that the extant lineages immediately preceding and succeeding this transition harbor an exceptional number of transposable elements and it is tempting to speculate that these sequences might have catalyzed the adaptations that enabled vertebrates to venture into land. Here, we review the genome dynamics associated with the major transitions in vertebrate evolution and discuss how the highly repetitive genomic landscapes revealed by recent efforts to characterize the genomes of amphibians and sarcopterygians argue for turbulent genome dynamics occurring before the water-to-land transition and possibly enabling it.

Anakinra versus Baricitinib: Different Strategies for Patients Hospitalized with COVID-19.

BACKGROUND: Immunomodulatory drugs have been used in patients with severe COVID-19. The objective of this study was to evaluate the effects of two different strategies, based either on an interleukin-1 inhibitor, anakinra, or on a JAK inhibitor, such as baricitinib, on the survival of patients hospitalized with COVID-19 pneumonia. METHODS: Individuals admitted to two hospitals because of COVID-19 were included if they fulfilled the clinical, radiological, and laboratory criteria for moderate-to-severe disease. Patients were classified according to the first immunomodulatory drug prescribed: anakinra or baricitinib. All subjects were concomitantly treated with corticosteroids, in addition to standard care. The main outcomes were the need for invasive mechanical ventilation (IMV) and in-hospital death. Statistical analysis included propensity score matching and Cox regression model. RESULTS: The study subjects included 125 and 217 individuals in the anakinra and baricitinib groups, respectively. IMV was required in 13 (10.4%) and 10 (4.6%) patients, respectively (p = 0.039). During this period, 22 (17.6%) and 36 (16.6%) individuals died in both groups (p = 0.811). Older age, low functional status, high comorbidity, need for IMV, elevated lactate dehydrogenase, and use of a high flow of oxygen at initially were found to be associated with worse clinical outcomes. No differences according to the immunomodulatory therapy used were observed. For most of the deceased individuals, early interruption of anakinra or baricitinib had occurred at the time of their admission to the intensive care unit. CONCLUSIONS: Similar mortality is observed in patients treated with anakinra or baricitinib plus corticosteroids.