Memoria del Tribunal Tutelar de Menores de Pamplona : 1924-1928

En cub.: Cinco años de vidaMención de responsabilidad tomada de fin del textoFecha tomada de p. [3], 192

Two cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma

There is a paucity of adequate mouse models and cell lines available to study lung squamous cell carcinoma (LUSC). We have generated and characterized two models of phenotypically different transplantable LUSC cell lines, i.e. UN-SCC679 and UN-SCC680, derived from A/J mice that had been chemically induced with N-nitroso-tris-chloroethylurea (NTCU). Furthermore, we genetically characterized and compared both LUSC cell lines by performing whole-exome and RNA sequencing. These experiments revealed similar genetic and transcriptomic patterns that may correspond to the classic LUSC human subtype. In addition, we compared the immune landscape generated by both tumor cells lines in vivo and assessed their response to immune checkpoint inhibition. The differences between the two cell lines are a good model for the remarkable heterogeneity of human squamous cell carcinoma. Study of the metastatic potential of these models revealed that both cell lines represent the organotropism of LUSC in humans, i.e. affinity to the brain, bones, liver and adrenal glands. In summary, we have generated valuable cell line tools for LUSC research, which recapitulates the complexity of the human disease.This work was supported by FIMA, Centro de Investigacion Biomedica en Red de Cancer (CIBERONC) (grant number: CB16/12/00443), Fundacion Cientifica Asociacion Espanola Contra el Cancer (grant number: GCB14-2170), Fundacion Ramon Areces, Instituto de Salud Carlos III and the European Regional Development Fund (ERDF, A way to make Europe) (grant numbers: PI19/00098; PI19/00230; PI20/00419), Fundacion Roberto Arnal Planelles and an IASLC Fellowship funding (K.V.); D.S. was supported by the Juan de la Cierva-Incorporacion program, Spanish Ministry of Science and Innovation (grant number: IJCI-2016-27595); E.R. was supported by a FPU, Spanish Ministry of Education ( grant number: FPU17/01168); M.E. was supported by PFIS, Spanish Ministry of Health, M.L. was supported by a Junior Investigator grant from AECC

Investment in the long-tail of biodiversity data: from local research to global knowledge

In business, the "long-tail economy" refers to a market strategy where the gravity center shifts from a few high-demand products to many, varied products focused on small niches. Commercialization of individually low-demand products can be profitable as long as their production cost is low and, all taken together, they aggregate into a big chunk of the market. Similarly, in the "business" of biodiversity data acquisition, we can find several mainstream products that produce zillions of bits of information every year and account for most of the budget allocated to increase our primary data-based knowledge about Earth's biological diversity. These products play a crucial role in biodiversity research. However, along with these large global projects, there is a constellation of small-scale institutions that work locally, but whose contribution to our understanding of natural processes should not be dismissed. These information datasets can be collectively referred to as the "long-tail biodiversity data"

Arañas de Navarra. Diversidad y distribución. Métodos digitales de estudio

La idea primera que llevó a iniciar este trabajo de tesis fue la de hacer un gran muestreo de arañas de Navarra; escribir algo imposible que contuviera improbablemente todas las arañas dentro. Si estuvieran quietas. Se diseñó un esquema de muestreo casi redondo, un abanico de posibles combinaciones que luciera bien y sonara coherente. Se hicieron luego miles de kilómetros por carreteras y caminos, cientos de litros de agua llovida en las trampas y en las botas. Laboratorio, lupa, microscopio, 23 000 arañas. Y un día el muestreo se acaba, y cuando está uno analizando muestras piensa si no sería estupendo poner trampas de caída en los árboles, porque no están quietas, en verdad; y cuántas debe de haber bajo el suelo, y qué distintas. Y se da uno cuenta de que, efectivamente, tener todas las arañas es improbable, y escribirlo imposible

Preservation of Hippocampal Neuron Numbers and Hippocampal Subfield Volumes in Behaviorally Characterized Aged Tree Shrews

Aging is associated with a decreased ability to store and retrieve information. The hippocampal formation plays a critical role in such memory processes, and its integrity is affected during normal aging. We used tree shrews (Tupaia belangeri) as an animal model of aging, because in many characteristics, tree shrews are closer to primates than they are to rodents. Young and aged male tree shrews performed a holeboard spatial memory task, which permits assessment of reference and working memory. Upon completion of the behavioral measurements, we carried out modified stereological analyses of neuronal numbers in various subdivisions of the hippocampus and used the Cavalieri method to calculate the volumes of these subfields. Results showed that the working memory of aged tree shrews was significantly impaired compared with that of young animals, whereas the hippocampus-dependent reference memory remained unchanged by aging. Estimation of the number of neurons revealed preserved neuron numbers in the subiculum, in the subregions CA1, CA2, CA3, and in the hilus of the dentate gyrus. Volume measurements showed no aging-related changes in the volume of any of these hippocampal subregions, or in the molecular and granule cell layers of the dentate gyrus of tree shrews. We conclude that the observed changes in memory performance in aging tree shrews are not accompanied by observable reductions of hippocampal neuron numbers or hippocampal volume, rather, the changes in memory performance are more likely the result of modified subcellular mechanisms that are affected by the aging process.

Silica-induced Chronic Inflammation Promotes Lung Carcinogenesis in the Context of an Immunosuppressive Microenvironment

The association between inflammation and lung tumor development has been clearly demonstrated. However, little is known concerning the molecular events preceding the development of lung cancer. In this study, we characterize a chemically induced lung cancer mouse model in which lung cancer developed in the presence of silicotic chronic inflammation. Silica-induced lung inflammation increased the incidence and multiplicity of lung cancer in mice treated with N-nitrosodimethylamine, a carcinogen found in tobacco smoke. Histologic and molecular analysis revealed that concomitant chronic inflammation contributed to lung tumorigenesis through induction of preneoplastic changes in lung epithelial cells. In addition, silica-mediated inflammation generated an immunosuppressive microenvironment in which we observed increased expression of programmed cell death protein 1 (PD-1), transforming growth factor-β1, monocyte chemotactic protein 1 (MCP-1), lymphocyte-activation gene 3 (LAG3), and forkhead box P3 (FOXP3), as well as the presence of regulatory T cells. Finally, the K-RAS mutational profile of the tumors changed from Q61R to G12D mutations in the inflammatory milieu. In summary, we describe some of the early molecular changes associated to lung carcinogenesis in a chronic inflammatory microenvironment and provide novel information concerning the mechanisms underlying the formation and the fate of preneoplastic lesions in the silicotic lung

Longitudinal study of a mouse model of chronic pulmonary inflammation using breath hold gated micro-CT.

Abstract Objectives To evaluate the feasibility of using automatic quantitative analysis of breath hold gated micro-CT images to detect and monitor disease in a mouse model of chronic pulmonary inflammation, and to compare image-based measurements with pulmonary function tests and histomorphometry. Material and methods Forty-nine A/J mice were used, divided into control and inflammation groups. Chronic inflammation was induced by silica aspiration. Fourteen animals were imaged at baseline, and 4, 14, and 34 weeks after silica aspiration, using micro-CT synchronized with ventilator-induced breath holds. Lung input impedance was measured as well using forced oscillation techniques. Five additional animals from each group were killed after micro-CT for comparison with histomorphometry. Results At all time points, micro-CT measurements show statistically significant differences between the two groups, while first differences in functional test parameters appear at 14 weeks. Micro-CT measurements correlate well with histomorphometry and discriminate diseased and healthy groups better than functional tests. Conclusion Longitudinal studies using breath hold gated micro-CT are feasible on the silica-induced model of chronic pulmonary inflammation, and automatic measurements from micro-CT images correlate well with histomorphometry, being more sensitive than functional tests to detect lung damage in this model

Investment in the Long-Tail of Biodiversity Data: From local research to global knowledge

In business, the “long-tail economy” refers to a market strategy where the gravity center shifts from a few high-demand products to many, varied products focused on small niches. Commercialization of individually low-demand products can be profitable as long as their production cost is low and, all taken together, they aggregate into a big chunk of the market. Similarly, in the “business” of biodiversity data acquisition, we can find several mainstream products that produce zillions of bits of information every year and account for most of the budget allocated to increase our primary data-based knowledge about Earth’s biological diversity. These products play a crucial role in biodiversity research. However, along with these large global projects, there is a constellation of small-scale institutions that work locally, but whose contribution to our understanding of natural processes should not be dismissed. These information datasets can be collectively referred to as the “long-tail biodiversity data”. Here we present the case of the Museum of Sciences University of Navarra, which harbors the research activity of the Museum of Zoology (MZNA) and herbarium (PAMP) of the University of Navarra in Spain. For the last 40 years, its members have been involved in hundreds of research projects, from local to international level—but quantitatively, the vast majority of its biodiversity records come from Navarra, a smallish (10,000 sq. km) administrative region in the north of Spain. Despite its modest area, the available information about the region in the Museum database approaches one million records of thousands of species, including dozens of type series. Fifteen years ago, a series of national research grants enabled boosting digitization and public access to the database records through the Global Biodiversity Information Facility (GBIF). Although those grants were never renewed, the Museum continued its digitizing and standardizing program on vouchered collections, as well as sampling additional raw biodiversity data through long term ecological sites using the Museum’s resources, which annually provide thousands of new records at the local level. Currently, the Museum has already published through GBIF’s IPT (Integrated Publishing Toolkit) 30 datasets, containing more than half-million records of about 5700 taxa. Its records have contributed to more than 60 peer-reviewed publications over the last five years. Institutions that basically harvest biodiversity data at a local scale usually show a high degree of specialization, gathering researchers with strong (albeit often narrow) expertise in the taxonomy and ecology of nearby ecosystems. They are thus an extremely valuable tool when dealing with processes resulting in diversity changes that can be identified rather precisely, especially when their work can be traced back many decades. Making all this fine-scale information accessible and actionable requires, in most of the cases, a rather modest investment in staff training on data management (e.g., standards, database interoperability) or museum curation procedures, and on informatics infrastructure. As in the case of business, it is not a matter of choosing between producing blockbusters or independent cinema--but of leveraging available resources and maximizing output

Two cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma

There is a paucity of adequate mouse models and cell lines available to study lung squamous cell carcinoma (LUSC). We have generated and characterized two models of phenotypically different transplantable LUSC cell lines, i.e. UN-SCC679 and UN-SCC680, derived from A/J mice that had been chemically induced with N-nitroso-tris-chloroethylurea (NTCU). Furthermore, we genetically characterized and compared both LUSC cell lines by performing whole-exome and RNA sequencing. These experiments revealed similar genetic and transcriptomic patterns that may correspond to the classic LUSC human subtype. In addition, we compared the immune landscape generated by both tumor cells lines in vivo and assessed their response to immune checkpoint inhibition. The differences between the two cell lines are a good model for the remarkable heterogeneity of human squamous cell carcinoma. Study of the metastatic potential of these models revealed that both cell lines represent the organotropism of LUSC in humans, i.e. affinity to the brain, bones, liver and adrenal glands. In summary, we have generated valuable cell line tools for LUSC research, which recapitulates the complexity of the human disease