Los orígenes de un nuevo gen de diseño de alas de mariposa dentro de una familia de reguladores conservados del ciclo celular

A major challenge in evolutionary biology is to understand the origins of novel structures. The wing patterns of butterflies and moths are derived phenotypes unique to the Lepidoptera. Here we identify a gene that we name poikilomousa (poik), which regulates colour pattern switches in the mimetic Heliconius butterflies. Strong associations between phenotypic variation and DNA sequence variation are seen in three different Heliconius species, in addition to associations between gene expression and colour pattern. Colour pattern variants are also associated with differences in splicing of poik transcripts. poik is a member of the conserved fizzy family of cell cycle regulators. It belongs to a faster evolving subfamily, the closest functionally characterised orthologue being the cortex gene in Drosophila, a female germ-line specific protein involved in meiosis. poik appears to have adopted a novel function in the Lepidoptera and become a major target for natural selection acting on colour and pattern variation in this group

Impact of timing of stem cell return following high dose melphalan in multiple myeloma patients with renal impairment: a single center experience

High dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) remains the standard consolidation in transplant eligible multiple myeloma (MM) patients. The timing between HDM administration and hematopoietic stem cell return (HSCR) varies among institutions, with a 'rest period' of 48 hours (h) employed by some for patients with renal impairment (RI). We investigated the differences in hematopoietic recovery and HDM toxicity between MM patients with RI who had HSCR after 24 vs 48 h from HDM. Fifty MM patients with RI (48 h group; n = 31 and 24 h group; n = 19) were included. No statistically significant differences were noted in surrogates for hematopoietic recovery and HDM toxicity between both groups. Only one death occurred in the 24 h group. No patients required renal replacement therapy. Therefore, a 24 h period between HDM and AHSC infusion appears safe for MM patients with RI

Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real-world analysis of outcomes in 211 patients.

Funder: Janssen Pharmaceuticals; Id: http://dx.doi.org/10.13039/100008897Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse. We aimed to investigate outcomes and tolerability for ibrutinib when given second line in a real-world setting. Our multicentre retrospective analysis included 211 R/R MCL patients, median age 73 years, receiving ibrutinib second-line within the United Kingdom's National Health Service. Overall response to ibrutinib was 69% (complete response 27%). The median progression-free survival (PFS) was 17·8 months (95% CI 13·1-22·2) and median overall survival (OS) 23·9 months (95% CI 15·0-32·8). Drug-related adverse event led to dose reduction in 10% of patients and discontinuation in 5%. In patients with progressive disease, accounting for 100 of 152 patients stopping ibrutinib, 43% received further systemic therapy. Post-ibrutinib rituximab, bendamustine and cytarabine (R-BAC) showed a trend toward improved survival compared to alternative systemic treatments (post-ibrutinib median OS 14·0 months, 95% CI 8·1-19·8, vs. 3·6 months, 95% CI 2·6-4·5, P = 0·06). Our study confirms the clinical benefit and good tolerability of ibrutinib at first relapse in a real-world population. Patients progressing on ibrutinib had limited survival but outcomes with R-BAC in select patients were promising

Subtle Introgression Footprints at the End of the Speciation Continuum in a Clade of <i>Heliconius</i> Butterflies

Quantifying gene flow between lineages at different stages of the speciation continuum is central to understanding speciation. Heliconius butterflies have undergone an adaptive radiation in wing color patterns driven partly by natural selection for local mimicry. Color patterns are also known to be used as assortative mating cues. Therefore, wing pattern divergence is considered to play a role in speciation. A corollary is that mimicry between closely related species may be associated with hybridization and interfere with reproductive isolation. Here, we take a multifaceted approach to explore speciation history, species boundaries, and traits involved in species differentiation between the two closely related species, Heliconius hecale and Heliconius ismenius. We focus on geographic regions where the two species mimic each other and contrast this with geographic regions where they do not mimic each other. To examine population history and patterns of gene flow, we tested and compared a four-population model accounting for linked selection. This model suggests that the two species have remained isolated for a large part of their history, yet with a small amount of gene exchange. Accordingly, signatures of genomic introgression were small except at a major wing pattern allele and chemosensing genes and stronger in the mimetic populations compared with nonmimetic populations. Behavioral assays confirm that visual confusion exists but that short-range cues determine strong sexual isolation. Tests for chemical differentiation between species identified major differences in putative pheromones which likely mediate mate choice and the maintenance of species differences

Morphometric quantification of wing pattern used for QTL analysis

This file contains phenotypic data for QTL analysis of the three crosses. These data are derived from the morphometric quantification of wing pattern using Colour Pattern Modelling (CPM; Le Poul et al., 2014) and are given for each offspring as the principal components (PCs) derived from the Principal Component Analysis (PCA). Only axes explaining more than 1% of the variance are used. The number of specimens analysed for each brood is determined by the number of offspring used for the final linkage maps which have at least one intact forewing and one intact hindwing

Data from: Conservatism and novelty in the genetic architecture of adaptation in Heliconius butterflies

Understanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima

Efficacy of R-BAC in relapsed, refractory mantle cell lymphoma post BTK inhibitor therapy

Patients with mantle cell lymphoma progressing on Bruton's tyrosine kinase inhibitor (BTKi) have very poor prognosis and there is currently no standard of care. In this retrospective cohort study, patients progressing on BTKi received R-BAC (rituximab, bendamustine, cytarabine). Overall response rate was 83% (complete response 60%) and 31% were bridged to allogeneic stem cell transplant (alloSCT). Median progression-free survival was 101 months (95% confidence interval (CI) 6 center dot 9-13 center dot 3) and median overall survival was 12 center dot 5 months (95% CI 11 center dot 0-14 center dot 0). In those consolidated with alloSCT only one patient relapsed. R-BAC demonstrates a high response rate in the post-BTKi setting and in transplant eligible patients is an effective bridge to alloSCT

Genotypic data along the linkage maps used for QTL analysis

In this file, genotypic data for QTL analyses of the three crosses are given. Format of these data follows the input for R/qtl (Broman et al., 2003) with two segregating states (homozygous AA and heterozygous AB), accounting for male informative markers used for the QTL analysis (no intercross markers were used). The number of specimens analysed for each brood is determined by the number of offspring used for the final linkage maps which have at least one intact forewing and one intact hindwing

Los orígenes de un nuevo gen de diseño de alas de mariposa dentro de una familia de reguladores conservados del ciclo celular

A major challenge in evolutionary biology is to understand the origins of novel structures. The wing patterns of butterflies and moths are derived phenotypes unique to the Lepidoptera. Here we identify a gene that we name poikilomousa (poik), which regulates colour pattern switches in the mimetic Heliconius butterflies. Strong associations between phenotypic variation and DNA sequence variation are seen in three different Heliconius species, in addition to associations between gene expression and colour pattern. Colour pattern variants are also associated with differences in splicing of poik transcripts. poik is a member of the conserved fizzy family of cell cycle regulators. It belongs to a faster evolving subfamily, the closest functionally characterised orthologue being the cortex gene in Drosophila, a female germ-line specific protein involved in meiosis. poik appears to have adopted a novel function in the Lepidoptera and become a major target for natural selection acting on colour and pattern variation in this group