A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins

Despite their evolutionary, developmental, and functional importance the origin of vertebrate paired appendages remains uncertain. In mice, a single enhancer termed ZRS is solely responsible for Shh expression in limbs. Here, zebrafish and mouse transgenic assays trace the functional equivalence of ZRS across the gnathostome phylogeny. CRISPR/Cas9-mediated deletion of the medaka-ZRS and enhancer assays reveal the existence of ZRS shadow enhancers in both teleost and human genomes. Deletion of both ZRS and shadow ZRS abolish shh expression and completely truncate pectoral fin formation. Strikingly, deletion of ZRS results in an almost complete ablation of the dorsal fin. This finding indicates that a ZRS-Shh regulatory module is shared by paired and median fins, and that paired fins likely emerged by the co‐option of developmental programs established in the median fins of stem gnathostomes. Shh function was later reinforced in pectoral fin development with the recruitment of shadow enhancers, conferring additional robustness

The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan

The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ~267.9–248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell

Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey

There is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it

La secuenciación de los genomas de dos tortugas: Pelodiscus sinesis y Chelonia mydas

As is well known, evolution consists of descent with modification, which implies a very important fact in the evolutionary framework: that everything new derives from something old. However, this is not so clear for certain structures, which are called true innovations; that is, they do not clearly appear from the modification of a structure that was previously present. One of these structures is the turtle shell.Como es bien sabido, la evolución consiste en descendencia con modificación, lo cual implica un hecho muy importante en el marco evolutivo: que todo lo nuevo deriva de algo viejo. Sin embargo,&nbsp;&nbsp; esto no está tan claro para ciertas estructuras, las que se denominan innovaciones verdaderas; es decir, que no aparecen claramente a partir de la modificación de una estructura que estaba presente an- teriormente. Una de estas estructuras es el caparazón de la tortuga

Los complejos Hox como modelos de evolución genómica en cordados: Caracterización y regulación de la expresión del clúster Hox en el anfioxo europeo

[spa] Todos los animales, vivos y fósiles, están comprendidos dentro de 35 fila. Éstos abarcan la enorme diversidad de morfologías que se han generado durante la evolución animal, desde una medusa, hasta una mosca o nosotros mismos, el hombre. Cada una de las diferentes morfologías son en último término el resultado de un proceso de desarrollo embrionario muy finamente regulado en el que participan cientos de genes, y que forman parte de decenas de redes génicas que interactúan unas con otras. A lo largo del tiempo, estas morfologías han ido evolucionando de forma que se han ido generando nuevas especies a partir de otras preexistentes o ancestros, compartidos por las especies que derivan de él. Dado este marco, cobra fuerza una disciplina relativamente reciente, la Evo-Devo o Evolución del Desarrollo, que pretende explicar la evolución de la morfología animal buscando los cambios en los genes del desarrollo embrionario, ya que la primera es fruto del segundo. Sin embargo, la mayoría de los genes del desarrollo son los mismos en todos los animales, algo que se conoce como el toolkit genético, y esto lleva a lo que se conoce como la paradoja de la Evo-Devo: ¿cómo se explica entonces la gran diversidad morfológica, si los diferentes animales están construidos con los mismos genes? Hay que buscar por tanto las diferencias que existan en los procesos del desarrollo de los diferentes animales. Una de estas diferencias puede recaer en cómo los genes del desarrollo se regulan. En esta tesis, se han utilizado los genes Hox como modelos de evolución genómica, y se han analizado el patrón de expresión de estos genes en la especie europea de cefalocordado, Branchiostoma lanceolatum. Se ha identificado el patrón de expresión de casi todos los genes del clúster Hox de este animal, constituido por 15 genes Hox. De ellos, los genes Hox1, 2, 3, 4 y 6 ya estaban descritos en la especie americana B. floridae, aunque se ha encontrado un patrón diferente para el gen Hox6. Además, para los genes Hox6 y Hox14, se ha encontrado un patrón de regulación modular, donde parte del patrón de expresión está regulado por ácido retinóico. En otra fase de la tesis, se han identificado putativos elementos reguladores en las regiones intergénicas de estos genes mediante una estrategia de "phylogenetic footprinting". Esto ha sido realizado mediante la comparación de regiones ortólogas de los genes Hox de las dos especies de anfioxo y humando. Algunas de estas, como las que rodean el gen Hox4, están conservadas también con pez cebra, y son capaces de dirigir la expresión de un gen reporter en tejidos donde se expresan los genes endógenos. Además, siguiendo la misma estrategia, hemos identificado una región de regulación global que está presente en vertebrados, situándose su origen al menos en el ancestro de los cordados.[eng] "Hox complex as models for genomic evolution: characterization and regulation of Hox genes expression of European Hox cluster". Hox genes are key developmental genes involved in patterning the antero-posterior axis of most metazoans studied so far. They generally are linked in genomic cluster and expressed with spatial and temporal colinearity in amphioxus and vertebrates. The closer to the 3' extreme of the cluster the gene is, the earlier and more anteriorly it is expressed. Nonetheless, this is fully true for all genes only in vertebrate clusters, since the expression of almost all central and all posterior Hox genes of amphioxus, which represents the closest relative to the chordate ancestor, is not known, and the expression in hemichordates and tunicates is not always colinear. In this thesis, we present a complete expression profile of amphioxus Hox genes and interestingly report the breaking of both spatial and temporal colinearity of some central and posterior Hox genes. Posterior Hox genes are expressed in structures like the notochord and posterior parts of the gut. Hox14 had the most divergent expression pattern, being also present in the anterior cerebral vesicle and pharyngeal endoderm. This is the first report of Hox expression in the most anterior part of a central nervous system. We also show that Hox14 expression is partially regulated by retinoic acid (RA) (in notochord and hindgut), like it happens for more anterior Hox genes are. On the other hand, Hox14 expression in the cerebral vesicle and pharynx are not influenced by RA. The lack of constriction in the posterior part of vertebrate and cephalochordate Hox cluster may be the cause of their independent expansion and their co-option for patterning different structures, allowing the breaking of colinearity in deuterostomes

How Do Morphological Novelties Evolve? Novel Approaches to Define Novel Morphologies

Evolutionary innovations are biological revolutions: new organs are critically associated with the emergence of new species and their exploitation of new niches. Despite their importance in the history of life, how a morphological novelty arises and evolves is a long-standing question in evolutionary biology. By combining evolutionary theories with comparative developmental embryology, the emergence of the evo-devo discipline at the end of the twentieth century revived the interest in these questions. Mostly, a lack of appropriate techniques for non-model organisms precluded further advancements, and it is only now that novel DNA sequencing and genome editing techniques allow us to ask these long-standing questions in the organisms that may best serve to answer them. These new approaches have revealed the need of a new conceptual framework to define and classify morphological novelties in animal evolution. Thus, in this review, we will first revisit some of the most influential definitions of morphological novelty that have been coined over the last half century to further propose the use of the generative events that originated a new structure as the criterion to consider this new organ a morphological novelty or not. These generative events or phenomenological modes are divided into four different categories: (1) fusion of existing structures, (2) heterotopic activation of a gene regulatory network, (3) recruitment of additional cell types (either pre-existing or novel) into structures and (4) processes of symbiogenesis. We will finally revisit how recent studies have shed light into the mechanisms underpinning the evolutionary origin of some of the most classical morphological novelties