Genomics of Secondarily Temperate Adaptation in the Only Non-Antarctic Icefish

White-blooded Antarctic icefishes, a family within the adaptive radiation of Antarctic notothenioid fishes, are an example of extreme biological specialization to both the chronic cold of the Southern Ocean and life without hemoglobin. As a result, icefishes display derived physiology that limits them to the cold and highly oxygenated Antarctic waters. Against these constraints, remarkably one species, the pike icefish Champsocephalus esox, successfully colonized temperate South American waters. To study the genetic mechanisms underlying secondarily temperate adaptation in icefishes, we generated chromosome-level genome assemblies of both C. esox and its Antarctic sister species, Champsocephalus gunnari. The C. esox genome is similar in structure and organization to that of its Antarctic congener; however, we observe evidence of chromosomal rearrangements coinciding with regions of elevated genetic divergence in pike icefish populations. We also find several key biological pathways under selection, including genes related to mitochondria and vision, highlighting candidates behind temperate adaptation in C. esox. Substantial antifreeze glycoprotein (AFGP) pseudogenization has occurred in the pike icefish, likely due to relaxed selection following ancestral escape from Antarctica. The canonical AFGP locus organization is conserved in C. esox and C. gunnari, but both show a translocation of two AFGP copies to a separate locus, previously unobserved in cryonotothenioids. Altogether, the study of this secondarily temperate species provides an insight into the mechanisms underlying adaptation to ecologically disparate environments in this otherwise highly specialized group

Removing the bad apples: A simple bioinformatic method to improve loci-recovery in de novo RADseq data for non-model organisms

1. The restriction site-associated DNA (RADseq) family of protocols involves digesting DNA and sequencing the region flanking the cut site, thus providing a cost and time-efficient way for obtaining thousands of genomic markers. However, when working with non-model taxa with few genomic resources, optimization of RADseq wet-lab and bioinformatic tools may be challenging, often resulting in allele dropout—that is when a given RADseq locus is not sequenced in one or more individuals resulting in missing data. Additionally, as datasets include divergent taxa, rates of dropout will increase since restriction sites may be lost due to mutation. Mitigating the impacts of allele dropout is crucial, as missing data may lead to incorrect inferences in population genetics and phylogenetics. 2. Here, we demonstrate a simple pipeline for the optimization of RADseq datasets which involves partitioning datasets into subgroups, namely by reducing and analysing the dataset at a population or species level. By running the software Stacks at a subgroup level, we were able to reliably identify and remove individuals with high levels of missing data (bad apples) likely stemming from artefacts in library preparation, DNA quality or sequencing artefacts. 3. Removal of the bad apples generally led to an increase in loci and decrease in missing data in the final datasets. 4. The biological interpretability of the data, as measured by the number of retrieved loci and missing data, was considerably increased

Sustained Shugoshin 1 downregulation reduces tumor growth and metastasis in a mouse xenograft tumor model of triple-negative breast cancer

Abstract Background Triple-negative breast cancer (TBNC) is an aggressive breast cancer subtype with a poor prognosis. Shugoshin-1 (SGO1) protects chromatids from early separation. Previous studies from our group have demonstrated that transient SGO1 downregulation suppresses early stages of metastasis (the epithelial-to-mesenchymal transition, or EMT, cell invasion, and cell migration) in TNBC cells. Thus, the inhibition of SGO1 activity may represent a potential therapeutic intervention against cancers that progress to metastasis. Therefore, we aimed to investigate the effects of sustained shRNA-mediated SGO1 downregulation on tumor growth and metastasis in TBNC. To that end, female NOD-SCID Gamma (NSG) mice were injected with 2.5 × 106 shRNA Control (n = 10) or shRNA SGO1 (n = 10) MDA-MB-231 cells. After eight weeks, the number of mice with metastasis to the lymph nodes was calculated. Primary and metastatic tumors, as well as lung and liver tissue, were harvested, measured, sectioned, and stained with hematoxylin and eosin (H&E) stain. Results Tumor growth and metastasis to the lymph nodes and lungs were significantly reduced in the shRNA SGO1-treated mice group, while metastasis to the liver tends to be lower in cells with downregulated SGO1, but it did not reach statistical significance. Furthermore, sustained SGO1 downregulation significantly reduced cell proliferation, cell migration, and invasion which correlated with lower levels of Snail, Slug, MMP2, MMP3, and MMP9. Conclusion The supression of SGO1 activity in TNBC harboring dysregulated expression of SGO1 may be a potential target for preventing breast cancer growth and metastasis

Removing the bad apples: A simple bioinformatic method to improve loci-recovery in de novo RADseq data for non-model organisms

1. The restriction site-associated DNA (RADseq) family of protocols involves digesting DNA and sequencing the region flanking the cut site, thus providing a cost and time-efficient way for obtaining thousands of genomic markers. However, when working with non-model taxa with few genomic resources, optimization of RADseq wet-lab and bioinformatic tools may be challenging, often resulting in allele dropout—that is when a given RADseq locus is not sequenced in one or more individuals resulting in missing data. Additionally, as datasets include divergent taxa, rates of dropout will increase since restriction sites may be lost due to mutation. Mitigating the impacts of allele dropout is crucial, as missing data may lead to incorrect inferences in population genetics and phylogenetics. 2. Here, we demonstrate a simple pipeline for the optimization of RADseq datasets which involves partitioning datasets into subgroups, namely by reducing and analysing the dataset at a population or species level. By running the software Stacks at a subgroup level, we were able to reliably identify and remove individuals with high levels of missing data (bad apples) likely stemming from artefacts in library preparation, DNA quality or sequencing artefacts. 3. Removal of the bad apples generally led to an increase in loci and decrease in missing data in the final datasets. 4. The biological interpretability of the data, as measured by the number of retrieved loci and missing data, was considerably increased

Chromosome-Level Genome Assembly and Circadian Gene Repertoire of the Patagonia Blennie <i>Eleginops maclovinus</i>—The Closest Ancestral Proxy of Antarctic Cryonotothenioids

The basal South American notothenioid Eleginops maclovinus (Patagonia blennie or róbalo) occupies a uniquely important phylogenetic position in Notothenioidei as the singular closest sister species to the Antarctic cryonotothenioid fishes. Its genome and the traits encoded therein would be the nearest representatives of the temperate ancestor from which the Antarctic clade arose, providing an ancestral reference for deducing polar derived changes. In this study, we generated a gene- and chromosome-complete assembly of the E. maclovinus genome using long read sequencing and HiC scaffolding. We compared its genome architecture with the more basally divergent Cottoperca gobio and the derived genomes of nine cryonotothenioids representing all five Antarctic families. We also reconstructed a notothenioid phylogeny using 2918 proteins of single-copy orthologous genes from these genomes that reaffirmed E. maclovinus’ phylogenetic position. We additionally curated E. maclovinus’ repertoire of circadian rhythm genes, ascertained their functionality by transcriptome sequencing, and compared its pattern of gene retention with C. gobio and the derived cryonotothenioids. Through reconstructing circadian gene trees, we also assessed the potential role of the retained genes in cryonotothenioids by referencing to the functions of the human orthologs. Our results found E. maclovinus to share greater conservation with the Antarctic clade, solidifying its evolutionary status as the direct sister and best suited ancestral proxy of cryonotothenioids. The high-quality genome of E. maclovinus will facilitate inquiries into cold derived traits in temperate to polar evolution, and conversely on the paths of readaptation to non-freezing habitats in various secondarily temperate cryonotothenioids through comparative genomic analyses

Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker.

Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells. Immunohistochemistry staining of NSCLC tumor microarrays showed that strong phospho-Rb S249 staining positively correlated with tumor grade specifically in the squamous cell carcinoma (SCC) subtype. Strong immunoreactivity for p39 positively correlated with tumor stage, lymph node invasion, and distant metastases, also in SCC. Linear regression analyses showed that the combined scoring for phospho-Rb S249, p39 and E-cadherin in SCC is even more accurate at predicting tumor staging, relative to each score individually. We propose that combined immunohistochemistry staining of NSCLC samples for Rb phosphorylation on S249, p39, and E-cadherin protein expression could aid in the assessment of tumor staging and metastatic potential when tested in small primary tumor biopsies. The intense staining for phospho-Rb S249 that we observed in high grade SCC could also aid in the precise sub-classification of poorly differentiated SCCs

Geografía de la Salud sin fronteras, desde Iberoamérica

Este libro de Geografía sin fronteras, desde Iberoamérica, reúne trabajos de especialistas en materia de Geografía de la salud de países de Iberoamérica, con diversidad de enfoques y métodos, que permitirá al lector tener una visión del estado actual de esta rama holística e integral de la geografía y la importancia que tiene en la solución de problemas que aquejan nuestra sociedad. El libro se estructura en tres partes: la primera aborda aspectos epistemológicos, teórico conceptuales; en la segunda se presentan las aplicaciones de los SIG y aspectos metodológicos para abordar la salud púbica; y en la tercera se presentan estudios de caso. En la primera parte se aborda la epistemología de la Geografía de la salud: retos y convergencias; geografía y salud: integración de conocimientos y prácticas, como un modo de mirar hacia el mundo a partir de la geografía. Se desarrolla la dimensión local de lo cotidiano de la salud en el territorio; se abordan los procesos de urbanización y resultados en salud; se presenta el tema de la planeación estratégica, un nuevo pensamiento hacia la construcción de ciudades saludables; se abordan reflexiones sobre el estado del arte en la gestión municipal del riesgo de desastres en México. El último tema de esta primera parte del libro es sobre “La geografía médica de Jesús Galindo y Villa”, en el que se analizan los elementos que permitieron construir una cartografía desde la perspectiva de la Geografía de la Salud. La segunda parte del libro incluye aplicaciones de los SIG y metodologías. El primer trabajo es la metodología de evaluación multicriterio en el análisis espacial de la salud, cuyo objetivo es brindar elementos para el apoyo a la toma de decisiones que apunten a lograr una mejora en la calidad de vida de la población. Otra temática es la aplicación de las geo-tecnologías en la geografía de la salud, como los sistemas de información geográfica (SIG), los cuales se ha incrementado su uso en el campo de la salud en los últimos años. Las aplicaciones son muy diversas pueden utilizarse para trazar la ruta más efectiva que seguirá una ambulancia, para ubicar los servicios médicos de una ciudad, así como para analizar patrones de distribución de una determinada enfermedad. Se aborda el tema de tendencias y escenario para el 2020 de la diabetes mellitus en el Estado de México con el propósito es incentivar la iniciativa de políticas públicas que incidan en la disminución de esta enfermedad e impulsar estilos de vida más saludables, principalmente en municipios más vulnerables. La tercera parte del libro son estudios de caso de latitudes diferentes: de Puerto Rico, de México y de Chile, en los que se desarrollan las temáticas de riesgos naturales, vulnerabilidad, contaminación en ciudades, estilos de vida, espacios verdes y análisis espacial estadístico y comparativo de la práctica agroecológica. Exhortamos al lector a leer este valioso documento que le permitirá contar con bases teórico conceptuales, conocer algunas aplicaciones y tener una visión del potencial de la geografía de la salud. Agradecemos los valiosos aportes de los colegas participantes en esta obra, como una de las pocas en esta temática en idioma español y portugués, que sin duda seguirá fortaleciendo esta rama de la geografía. También agradecemos a las autoridades de la Facultad de Geografía de la Universidad Autónoma del Estado de México y de la Coordinación para la Innovación y la Aplicación de la Ciencia y la Tecnología de la Universidad Autónoma de San Luis Potosí, por el valioso apoyo brindado para la publicación de este libro

Voces y Visiones: Highlights from El Museo del Barrio\u27s Permanent Collection

Catalog for the exhibition Voces y Visiones: Highlights from El Museo del Barrio\u27s Permanent Collection held at the Seton Hall University Walsh Gallery, January 24 - May 13, 2005. Curated by Fatima Bercht, Deborah Cullen, Margarita Aguilar, and Noel Valentin. Includes essay and color illustrations