Hematopoietic stem cells under pressure.

"This is a non-final version of an article published in final form in Current Opinion in Hematology "PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including infection, inflammation, and exsanguination. HSCs possess the remarkable ability to reconstitute the entire hematopoietic system of an organism whose own hematopoietic system has been ablated. This ability is exploited routinely in the clinic via HSC transplantation (HSCT). Here, we focus on the physiological and molecular bottlenecks overcome by HSCs during transplantation. RECENT FINDINGS: During transplantation, HSCs encounter a damaged bone marrow niche, characterized molecularly by increases in oxygen concentrations and an altered cytokine milieu. New mechanisms and pathways have been recently implicated during HSCT, including transplanted HSC-dependent secretion of conditioning molecules that facilitate engraftment and pathways that protect HSCs from perturbed organelle homeostasis. SUMMARY: Better understanding the molecular processes HSCs employ to withstand the stress of transplant will illuminate novel targets for further improving conditioning regimens and engraftment during HSCT

Haematopoietic stem cell health in sickle cell disease and its implications for stem cell therapies and secondary haematological disorders.

Gene modification of haematopoietic stem cells (HSCs) is a potentially curative approach to sickle cell disease (SCD) and offers hope for patients who are not eligible for allogeneic HSC transplantation. Current approaches require in vitro manipulation of healthy autologous HSC prior to their transplantation. However, the health and integrity of HSCs may be compromised by a variety of disease processes in SCD, and challenges have emerged in the clinical trials of gene therapy. There is also concern about increased susceptibility to haematological malignancies during long-term follow up of patients, and this raises questions about genomic stability in the stem cell compartment. In this review, we evaluate the evidence for HSC deficits in SCD and then discuss their potential causation. Finally, we suggest several questions which need to be addressed in order to progress with successful HSC manipulation for gene therapy in SCD

Clones assemble! The clonal complexity of blood during ontogeny and disease.

Hematopoietic stem and progenitor cells (HSPCs) govern the daily expansion and turnover of billions of specialized blood cells. Given their clinical utility, much effort has been made toward understanding the dynamics of hematopoietic production from this pool of stem cells. An understanding of hematopoietic stem cell clonal dynamics during blood ontogeny could yield important insights into hematopoietic regulation, especially during aging and repeated exposure to hematopoietic stress-insults that may predispose individuals to the development of hematopoietic disease. Here, we review the current state of research regarding the clonal complexity of the hematopoietic system during embryogenesis, adulthood, and hematologic disease

Pyrolytic characterization of humic acids in relation to carbon sequestration mechanisms in representative soils from the basque country (Northern Spain)

Comunicación y póster presentados al citado simposio, celebrado del 17-20 de septiembre, 2002, en Leoben (Austria).Curie-Point analytical pyrolysis was used for the assessment of soil organic matter accumulation processes in representative ecosystems from the Basque Country (Northem Spain). The aim of the study is to identify the main mechanisms of carbon sequestration by carrying out a semiquantitative appraisal of biogeochemical processes ranging from selective preservation of plant macromolecular material to complex processes involving extensive depolymerization of plant-inherited constituents followed by synthesis of humic-type substances.Peer reviewe

Therapeutic molecules for osteoarthritis treatment. role of phloretin, ipriflavone and raloxifene in lipopolysaccharide induced osteoarthritic chondrocytes

Purpose: The search of novel molecules for the treatment of osteoarthritis (OA) is complex as any new therapeutic approach should encompass these requirements: inhibition of cartilage degradation, protection of bone and inhibition of inflammation. In the last years, different drugs have been proposed though most of them did not succeed in fulfil these requirements. Moreover, few of them have been encapsulated in drug delivery systems to improve their therapeutic potential to achieve a sustained or controlled release compared to the administration of equivalent doses of the free compounds. Nanoscience has arisen in the last decades as a potential field of study in drug delivery because nanomaterials may overcome the main current limitations to achieve an efficient and localized drug delivery by improving the targeted delivery and providing a sustained or controlled delivery to prolong the therapeutic effect. On the other hand, different polyphenols and aromatic organic compounds are known to possess anti-inflammatory, antioxidant and bone density-building properties..

OxyEMG: an application for determination of the oxyspinel group end-members based on electron microprobe analyses

The Oxyspinel group End-Member Generator (OxyEMG) is an improved version of the EMG application. This new version allows for calculating, based on electron microprobe analysis (EMPA), the proportions of 31 end-member components in an oxyspinel composition. These components are MgAl2O4 (spinel), FeAl2O4 (hercynite), MnAl2O4 (galaxite), ZnAl2O4 (gahnite), NiAl2O4 (chihmingite), CuAl2O4 (thermaerogenite), MgFe2O4 (magnesioferrite), Fe3O4 (magnetite), MnFe2O4 (jacobsite), ZnFe2O4 (franklinite), NiFe2O4 (trevorite), CuFe2O4 (cuprospinel), FeMn2O4, MgMn2O4, Mn3O4 (hausmannite), ZnMn2O4 (hetaerolite), MgCr2O4 (magnesiochromite), FeCr2O4 (chromite), MnCr2O4 (manganochromite), ZnCr2O4 (zincochromite), NiCr2O4 (nichromite), CoCr2O4 (cochromite), MgV2O4 (magnesiocoulsonite), FeV2O4 (coulsonite), MnV2O4 (vuorelainenite), Co3O4 (guite), TiMg2O4 (qandilite), TiFe2O4 (ulvöspinel), SiMg2O4 (ringwoodite), SiFe2O4 (ahrensite) and GeFe2O4 (brunogeierite). Compared with the older version, OxyEMG allows for (a) calculating 12 additional oxyspinel group end-member compositions (chihmingite, thermaerogenite, hausmannite, hetaerolite, FeMn2O4, MgMn2O4, cuprospinel, cochromite, guite, ringwoodite, ahrensite and brunogeierite), (b) discriminating the cation valency not only for Fe2+–Fe3+ but also for Mn2+–Mn3+ and Co2+–Co3+, and (c) changing the method to calculate the components of the magnetite and ulvöspinel prisms. As in EMG, this new version is an application that does not require an installation process and was created with the purpose of performing calculations to obtain cation proportions (per formula unit, p.f.u.), end-members of the oxyspinel group, a ΣR3+ value, a ΣR2+ value, ΣR3+ / ΣR2+ ratios, redistribution proportions for the corresponding end-members in the magnetite or ulvöspinel prisms, and a data validation section to check the results.</p

Upstream migration of anadromous and potamodromous brown trout: patterns and triggers in a 25-year overview

Producción CientíficaRiver fragmentation and alterations in flow and thermal regimes are the main stressors affecting migrating fish, which could be aggravated by climate change and increasing water demand. To assess these impacts and define mitigation measures, it is vital to understand fish movement patterns and the environmental variables affecting them. This study presents a long-term (1995–2019) analysis of upstream migration patterns of anadromous and potamodromous brown trout in the lower River Bidasoa (Spain). For this, captures in a monitoring station were analyzed using Survival Analysis and Random Forest techniques. Results showed that most upstream movements of potamodromous trout occurred in October–December, whereas in June–July for anadromous trout, although with differences regarding sex and size. Both, fish numbers and dates varied over time and were related to the environmental conditions, with different influence on each ecotype. The information provided from comparative studies can be used as a basis to develop adaptive management strategies to ensure freshwater species conservation. Moreover, studies in the southern distribution range can be crucial under climate warming scenarios, where species are expected to shift coldwards.Proyecto de innovación docente de la Universidad de Valladolid (PIF-UVa 2017)Ministerio de Ciencia, Innovación y Universidades (grant PTQ2018-010162)Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

VISUEL: un tablero dinámico web para la visualización de datos

Data visualization aims to explore and analyze data quickly, interactively, and intuitively using visual representations. Faced with the constant growth of data in terms of volume and diversity, visualization techniques must confront the challenge of dealing with increasingly large datasets in terms of representation, interaction, and performance. Therefore, these techniques must be able to effectively convey the characteristics of the information space and inspire discovery. In this article, a web dynamic dashboard for data visualization called VISUEL is presented. VISUEL supports multiple coordinated views, integrating visualization techniques such as scatterplots, parallel coordinates, and box plots, and interactive schematic maps to represent information enriched with spatial references. VISUEL is fully interactive, supporting traditional interactions like filtering, selection, brushing and linking, and zooming, among others. It also allows the user to configure the visual representation of their data, by selecting the color and shape of the representations. The usefulness of this tool is illustrated using real-life dataset related to the wine industry in Argentina. Important aspects of the case study are discovered through the construction and analysis of multiple views.La visualización de datos tiene como objetivo explorar y analizar los datos de forma rápida, interactiva e intuitiva mediante representaciones visuales. Ante el constante crecimiento de los datos en términos de volumen y diversidad, las técnicas de visualización deben afrontar el desafío de lidiar con conjuntos de datos cada vez más grandes en términos de representación, interacción y desempeño. Por lo tanto, estas técnicas deben ser capaces de transmitir de manera efectiva las características del espacio de información e inspirar el descubrimiento. En este artículo, se presenta un tablero web dinámico para la visualización de datos llamado VISUEL. VISUEL admite múltiples vistas coordinadas, integrando técnicas de visualización como diagramas de dispersión, coordenadas paralelas, diagramas de caja, y mapas esquemáticos interactivos para representar información enriquecida con referencias espaciales. VISUEL es totalmente interactivo y admite interacciones tradicionales como filtrado, selección, brushing and linking, y zoom, entre otras. También permite al usuario configurar la representación visual de sus datos, seleccionando el color y la forma de las representaciones. La utilidad de esta herramienta se ilustra utilizando datos reales relacionados con la industria del vino en Argentina. Se descubren aspectos importantes del caso de estudio mediante la construcción y el análisis de múltiples vistas.Facultad de Informátic

The global clonal complexity of the murine blood system declines throughout life and after serial transplantation.

Although many recent studies describe the emergence and prevalence of "clonal hematopoiesis of indeterminate potential" in aged human populations, a systematic analysis of the numbers of clones supporting steady-state hematopoiesis throughout mammalian life is lacking. Previous efforts relied on transplantation of "barcoded" hematopoietic stem cells (HSCs) to track the contribution of HSC clones to reconstituted blood. However, ex vivo manipulation and transplantation alter HSC function and thus may not reflect the biology of steady-state hematopoiesis. Using a noninvasive in vivo color-labeling system, we report the first comprehensive analysis of the changing global clonal complexity of steady-state hematopoiesis during the natural murine lifespan. We observed that the number of clones (ie, clonal complexity) supporting the major blood and bone marrow hematopoietic compartments decline with age by ∼30% and ∼60%, respectively. Aging dramatically reduced HSC in vivo-repopulating activity and lymphoid potential while increasing functional heterogeneity. Continuous challenge of the hematopoietic system by serial transplantation provoked the clonal collapse of both young and aged hematopoietic systems. Whole-exome sequencing of serially transplanted aged and young hematopoietic clones confirmed oligoclonal hematopoiesis and revealed mutations in at least 27 genes, including nonsense, missense, and deletion mutations in Bcl11b, Hist1h2ac, Npy2r, Notch3, Ptprr, and Top2b