Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

La lógica de los genomas

La publicación profundiza sobre uno de los grandes desafíos de la ciencia actual: la posibilidad de modificar los organismos desde su base. Desarrolla temas como la caracterización del ADN, la secuenciación genómica, las tecnologías de manipulación y edición de genes y las consecuencias que conlleva este nuevo conocimiento para la humanidad. La publicación plantea que en la actualidad existen dos elementos que están revolucionando la genética y genómica. El primero es la baja considerable del costo de secuenciar un genoma. Este proceso es el que permite conocer en detalle las enfermedades y características de un individuo. El segundo es la edición genómica, la que a través de herramientas moleculares facilita la entrada al genoma para realizar cambios y reparar anomalías que causan enfermedades

Peripheral macrophages promote tissue regeneration in zebrafish by fine-tuning the inflammatory response

Copyright © 2019 Morales and Allende. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The role of macrophages during regeneration in zebrafish has been well-documented. Nevertheless, new evidence indicates that zebrafish macrophages are a heterogeneous population of cells, and that they can play different roles during immune responses and in tissue restoration after damage and infection. In this work, we first aimed to classify zebrafish macrophages according to their distribution in the larva during homeostasis and after tissue damage, distinguishing peripheral, and hematopoietic tissue resident macrophages. We discovered differences between the migratory behavior of these two macrophage populations both before and after tissue damage, triggered by the amputation of the tail fin. Further, we found a specific role for peripheral tissue-resident macrophages, and we propose that these cells contribute to tail fin regeneration by down-regulating inflammatory mediators such as interleukin-1b (il1b) and by diminishing reactive oxygen species (ROS) in the damage site. Our work suggests that specific macrophage populations recruited after tissue damage in zebrafish larvae can display different functions during both inflammation and tissue regeneration

Elongator subunit 3 (Elp3) Is required for Zebrafish trunk development

Transfer RNAs (tRNAs) are the most post-transcriptionally modified RNA species. Some of these modifications, especially the ones located in the anti-codon loop, are required for decoding capabilities of tRNAs. Such is the case for 5-methoxy-carbonyl-methyl-2-thio-uridine (mcm(5)s(2)U), synthetized by the Elongator complex. Mutants for its sub-units display pleiotropic phenotypes. In this paper, we analyze the role of elp3 (Elongator catalytic sub-unit) in zebrafish development. We found that it is required for trunk development; elp3 knock-down animals presented diminished levels of mcm(5)s(2)U and sonic hedgehog (Shh) signaling activity. Activation of this pathway was sufficient to revert the phenotype caused by elp3 knockdown, indicating a functional relationship between Elongator and Shh through a yet unknown molecular mechanism.Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) CONICYT FONDECYT 3160326 Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) CONICYT FONDECYT 1180606 Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) CONICYT FONDAP 1509000

From Devo to Evo: patterning, fusion and evolution of the zebrafish terminal vertebra

Background With more than 30,000 species, teleosts comprise about half of today's living vertebrates, enriched with a wide set of adaptations to all aquatic systems. Their evolution was marked by modifications of their tail, that involved major rearrangements of the metameric organization of the axial skeleton. The most posterior or ural caudal skeleton, primitively included more than 10 vertebrae and, through a series of fusions and losses, became reduced to a single vertebra in modern ostariophysans, one of the largest clades of teleosts. The ontogeny of the ostariophysan Danio rerio recapitulates this process by forming two or three separate vertebrae that become a single vertebra in adults. We characterize the developmental sequence of this change by describing the processes of patterning, fusion and differential growth on each of the constitutive elements that sculpt the adult terminal vertebra. Results The ontogenetic changes of the terminal vertebra were characterized, highlighting their shared and derived characters in comparison with other teleosts. In zebrafish, there is: i) a loss of the preural centrum 1, ii) the formation of an hourglass-shaped autocentrum only in the anterior but not the posterior border of the compound centrum, iii) the formation of a vestigial posterior centrum that does not form an autocentrum and becomes incorporated beneath the compound centrum during development, and iv) the elongated dorso-posterior process of the compound centrum or pleurostyle appears as an independent element posterior to the compound centrum, before fusing to the ural neural arches and the anterior portion of the compound centrum. Conclusions The unique features of the formation of the terminal vertebra in Danio rerio reflect the remarkable changes that occurred during the evolution of teleosts, with potential shared derived characteristics for some of the major lineages of modern teleosts. A new ontogenetic model is proposed to illustrate the development of the terminal vertebra, and the phylogenetic implications for the evolution of caudal skeleton consolidation in ostariophysans are discussed.National Science Foundation (NSF) ANID/FONDAP/15090007 ANID/FONDECYT/1180606 043162 ANID/DOCTORADO NACIONAL/2015-2115078

Expression and splice variant analysis of the zebrafish tcf4 transcription factor

Wnt signalling has been implicated in antero-posterior patterning of the vertebrate embryonic body axis and in a number of other developmental processes. One of the downstream effectors of Wnt signalling is the β-catenin protein which complexes with members of the Lef/tcf transcription factor family. In the zebrafish, specification of the head has been shown to be dependent on the Tcf3 protein which acts as a repressor of the posteriorizing activity of Wnt (Nature 407 (2000) 913). Here, we report the cloning and expression pattern of the zebrafish tcf4 gene. In embryos, we find that the tcf4 gene is highly regulated at the level of RNA splicing such that the variant proteins that are produced contain or lack domains proposed to be essential in repression or activation of transcription. Expression of tcf4 mRNA is first detected in a graded fashion in the anterior brain and subsequently becomes restricted to the dorsal diencephalon and anterior midbrain. There is also transient expressi

Zebrafish cnbp Intron1 Plays a Fundamental Role in Controlling Spatiotemporal Gene Expression During Embryonic Development

Cellular nucleic acid binding protein (CNBP) is a strikingly conserved zinc-finger nucleic acid chaperone required for forebrain development. Its depletion causes forebrain truncation mainly as a consequence of a reduction in size of craniofacial structures and neural crest derivatives. The CNBP expression pattern is complex and highly dynamic, but little is known of the underlying mechanisms regulating its spatiotemporal pattern. CNBP expression is highly conserved between all vertebrates characterized. In this study we have combined comparative sequence analysis and in vivo testing of DNA fragments in zebrafish to identify evolutionarily constrained regulatory motifs that likely control expression of the cnbp gene in embryos. We found a novel exon sequence located 50 upstream of the Exon1-sequence reported in most databases, and two transcription start sites that generate two primary-transcripts that differ in their 50UTRs and expression profile during zebrafish embryonic development. Furthermore, we found a region inside the intron1 sequence that controls the cnbp developmental- specific transcriptional activation. Conserved binding sites for neural crest transcription factors were identified in this region. Mutagenesis analysis of the regulatory region revealed that Pax6/FoxD3 binding sites are required for proper zygotic cnbp expression. This is the first study that identifies, in vivo, cis-regulatory sequences inside intron sequences and typical neural crest transcription factors involved in cnbp spatiotemporal specific transcriptional control during vertebrate embryonic development.This work was supported by ANPCyT (PICT 00648 to N.B. Calcaterra), Josefina Prats Foundation (to A.M.J. Weiner), ICM (p06-039F to M.L. Allende), and FONDECYT (1070867 to M.L. Allende)

A Reliable Preclinical Model to Study the Impact of Cigarette Smoke in Development and Disease

The World Health Organization has estimated that, worldwide, cigarette smoking has caused more than 100 million deaths in the last century, a number that is expected to increase in the future. Understanding cigarette smoke toxicity is key for research and development of proper public health policies. The current challenge is to establish a reliable preclinical model to evaluate the effects of cigarette smoke. In this work, we describe a simple method that allows for quantifying the toxic effects of cigarette smoke using zebrafish. Here, viability of larvae and adult fish, as well as the effects of cigarette smoke extracts on vascular development and tissue regeneration, can be easily assayed. © 2019 by John Wiley & Sons, Inc

A novel in vivo model to study impaired tissue regeneration mediated by cigarette smoke

Cigarette smoke is associated with several pathologies including chronic respiratory diseases and cancer. In addition, exposure to cigarette smoke is correlated with impaired wound healing, where a significant decrease in the regenerative capacity of smokers is well documented and broadly considered a negative risk factor after trauma or surgery. So far, some in vitro and in vivo models have been described to study how exposure to cigarette smoke diminishes the regenerative potential in different organisms. However, although useful, many of these models are difficult and expensive to implement and do not allow high-throughput screening approaches. In order to establish a reliable and accessible model, we have evaluated the effects of cigarette smoke extract (CSE) on zebrafish development and regeneration. In this work, zebrafish embryos and larvae were exposed to low doses of aqueous CSE showing severe developmental abnormalities in a dose-dependent manner. Furthermore, when adult zebrafish were subjected to caudal fin amputation, we observed a significant decrease in the regenerative capacity of animals exposed to CSE. The effect was exacerbated in male and aged fish compared to female or young organisms. The establishment of a zebrafish model to assess the consequences of cigarette smoke and its effects on animal physiology could provide a new tool to study the underlying mechanisms involved in impaired tissue regeneration, and aid the development of novel approaches to treat complications associated with cigarette smoke toxicity.Entidad financiadora: Comision Nacional de Ciencia y Tecnologia (CONICYT), Chile - FONDECYT 1160270 ; FONDAP : 15090007 ; FONDECYT - 3160086

γ-Tubulin small complex formation is essential for early zebrafish embryogenesis

© 2018 The centrosomal protein γ-tubulin is part of the cytoplasmic γ-tubulin small (γ-TuSCs) and large complexes (γ-TuRCs). Both, molecular and cellular evidence indicate that γ-tubulin plays a central role in microtubule nucleation and mitotic spindle formation. However, the molecular mechanisms of complex formation and subsequent biological roles in animal development remain unclear. Here, we used γ-tubulin gene knockdown in the zebrafish early embryo model to gain insights into its activity and cellular contribution during vertebrate embryogenesis. γ-Tubulin loss-of-function impaired γ-TuSC formation, impacting the microtubule nucleation rate in vitro. Moreover, decreased γ-tubulin synthesis caused dramatic defects in nuclear dynamics and cell cycle progression, leading to developmental arrest at the mid-gastrula stage. At the subcellular level, microtubule organization and function were altered, affecting chromosome segregation and triggering cell proliferation arrest and apoptos