Proteostasis of aging and stem cells

Estudi realitzat a partir d’una estada a la the Salk Institute, Estats Units, entre 2010 i 2012. L'estabilitat del genoma és essencial per a la supervivència de les cèl • lules mare, però, l'estabilitat del proteoma pot tenir un paper igualment important en la identitat de cèl • lules mare i la seva funció. La nostra hipòtesi és que les cèl • lules mare tenen la capacitat de proteostasis augmentada en comparació amb els seus homòlegs diferenciats i ens varem preguntar si l'activitat del proteasoma és diferent a les cèl • lules mare embrionàries humanes (hESCs). En particular, els nostres resultats mostren que les poblacions de cèl• lules mare presenten una activitat del proteasoma que es correlaciona amb majors nivells de la subunitat 19S del proteasoma PSMD11/RPN-6 i un corresponent augment del ensamblatge del 26S/30S proteasoma. L'expressió ectòpica de PSMD11 és suficient per augmentar l'activitat del proteasoma. Sorprenentment, varem trobar que la llarga vida del GLP-1 C. elegans mutant té també un augment dramàtic en l'activitat del proteasoma associat a nivells augmentats en l'expressió de RPN-6. El factor de transcripció DAF-16 és essencial per l'augment de la longevitat de GLP-1 i els cucs mutants que trobem DAF-16 necessari per a l'augment d'expressió de RPN-6 i, per tant, per l'activació de l'activitat del proteasoma en GLP-1 mutant animals. Una possibilitat interessant és que els gens que regulen la vida i la resistència a l'estrès en C. elegans poden també regular la funció hESCs de mamífer, cèl • lules que son considerades immortals. Aquests resultats ens van portar a la conclusió de que FOXO4, un factor de transcripció sensible a la insulina/IGF-1, regula l'activitat del proteasoma en hESCs, el que suggereix un paper per FOXO4 en la funció d’aquestes cèl • lules. En efecte, FOXO4 es necessari per a la diferenciació en llinatges neuronals de les hESCs. Els nostres resultats estableixen una nova regulació de laproteostasis en hESCs que uneix la longevitat i la resistència a l'estrès en invertebrats amb la funció i identitat de les hESCs.

Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications

Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications.

JNK controls the onset of mitosis of planarian stem cells and triggers apoptotic cell death required for regeneration and remodeling

Regeneration of lost tissues depends on the precise interpretation of molecular signals that control and coordinate the onset of proliferation, cellular differentiation and cell death. However, the nature of those molecular signals and the mechanisms that integrate the cellular responses remain largely unknown. The planarian flatworm is a unique model in which regeneration and tissue renewal can be comprehensively studied in vivo. The presence of a population of adult pluripotent stem cells combined with the ability to decode signaling after wounding enable planarians to regenerate a complete, correctly proportioned animal within a few days after any kind of amputation, and to adapt their size to nutritional changes without compromising functionality. Here, we demonstrate that the stress-activated c-jun-NH2-kinase (JNK) links wound-induced apoptosis to the stem cell response during planarian regeneration. We show that JNK modulates the expression of wound-related genes, triggers apoptosis and attenuates the onset of mitosis in stem cells specifically after tissue loss. Furthermore, in pre-existing body regions, JNK activity is required to establish a positive balance between cell death and stem cell proliferation to enable tissue renewal, remodeling and the maintenance of proportionality. During homeostatic degrowth, JNK RNAi blocks apoptosis, resulting in impaired organ remodeling and rescaling. Our findings indicate that JNK-dependent apoptotic cell death is crucial to coordinate tissue renewal and remodeling required to regenerate and to maintain a correctly proportioned animal. Hence, JNK might act as a hub, translating wound signals into apoptotic cell death, controlled stem cell proliferation and differentiation, all of which are required to coordinate regeneration and tissue renewal.

Prácticas etnobotánicas e identidad cultural de las minorías étnicas de Yunnan

El trabajo de investigación aborda la evolución de las prácticas etnobotánicas (PEB) tradicionales, la evolución reciente de estas prácticas en un contexto de mutaciones en China en las últimas décadas y su valor como marcador de la identidad cultural (IC) de las minorías étnicas de la provincia China de Yunnan. Se trata de evaluar la realidad de la utilización, la preservación y la evolución de la etnomedicina en esta región y especialmente de las PEB, aclarar las relaciones que se pueden establecer entre la IC y las PEB y por lo tanto se estudian los nexos de unión entre las PEB y la IC de las minorías étnicas de Yunnan (MEY).

Federalism and democracy. The case of minority nations: a federalist deficit

In this chapter, after pointing out the different logics that lie behind the familiar ideas of democracy and federalism, I have dealt with the case of plurinational federal democracies. Having put forward a double criterion of an empirical nature with which to differentiate between the existence of minority nations within plurinational democracies (section 2), I suggest three theoretical criteria for the political accommodation of these democracies. In the following section, I show the agonistic nature of the normative discussion of the political accommodation of this kind of democracies, which bring monist and pluralist versions of the demos of the polity into conflict (section 3.1), as well as a number of conclusions which are the result of a comparative study of 19 federal and regional democracies using four analytical axes: the uninational/plurinational axis; the unitarianism-federalism axis; the centralisation-decentralisation axis; and the symmetry-asymmetry axis (section 3.2). This analysis reveals shortcomings in the constitutional recognition of national pluralism in federal and regional cases with a large number of federated units/regions with political autonomy; a lower degree of constitutional federalism and a greater asymmetry in the federated entities or regions of plurinational democracies. It also reveals difficulties to establish clear formulas in these democracies in order to encourage a “federalism of trust” based on the participation and protection of national minorities in the shared government of plurinational federations/regional states. Actually, there is a federal deficit in this kind polities according to normative liberal-democratic patterns and to what comparative analysis show. Finally, this chapter advocates the need for a greater normative and institutional refinement in plurinational federal democracies. In order to achieve this, it is necessary to introduce a deeper form of “ethical” pluralism -which displays normative agonistic trends, as well as a more “confederal/asymmetrical” perspective, congruent with the national pluralism of these kind of polities.

Three theories of liberalism for the three theories of federalism. A Hegelian turn

This paper links different political liberal theories, considered from the perspective of their moral ontology, with federal democracies. After giving a brief description of these theories, I discuss their relationship with the theoretical and institutional models of federalism. As methodological tools, the paper introduces some Hegel’s political concepts and deals with their potential application to the analysis of federalism, taken into account the case of minorities in multinational democracies. I postulate the need for a moral and institutional refinement of liberal-democratic patterns that is better able to accommodate national pluralism than has so far been achieved by traditional constitutionalism.

A programming environment having three levels of complexity for mobile robotics = Entorno de programación con tres niveles de complejidad para robótica móvil

This paper presents a programming environment for supporting learning in STEM, particularly mobile robotic learning. It was designed to maintain progressive learning for people with and without previous knowledge of programming and/or robotics. The environment was multi platform and built with open source tools. Perception, mobility, communication, navigation and collaborative behaviour functionalities can be programmed for different mobile robots. A learner is able to programme robots using different programming languages and editor interfaces: graphic programming interface (basic level), XML-based meta language (intermediate level) or ANSI C language (advanced level). The environment supports programme translation transparently into different languages for learners or explicitly on learners’ demand. Learners can access proposed challenges and learning interfaces by examples. The environment was designed to allow characteristics such as extensibility, adaptive interfaces, persistence and low software/hardware coupling. Functionality tests were performed to prove programming environment specifications. UV BOT mobile robots were used in these tests

Shading effects on the yield of an Argentinian wheat cultivar

Shading treatments of 50% of the incident radiation were applied to the semidwarf wheat cultivar Leones INTA before and after anthesis in two field experiments in Argentina in 1987 and 1988. The treatments reduced biological (above-ground dry matter) yield, grain yield and number of grains/m2. Number of grains/m2 was closely and linearly correlated with ear dry weight at anthesis and with the photothermal quotient, calculated from 20 days before to 10 days after anthesis. Grain yield was sink limited, and the shading treatments reduced sink strength. The contribution of preanthesis assimilates to grain yield was smaller in the shaded crops than in the unshaded controls; in unshaded crops, almost 40% of grain yield was contributed by preanthesis assimilates whilst in preanthesis shaded crops this contribution was negligible. The proportion of preanthesis assimilates contributed to the grain was closely related to the decrease in stem dry weight during grain filling. The effects of shading on main stems and tillers were the same.

Derivation of human embryonic stem cells at the center for regenerative medicine in Barcelona

We report here the legislative issues related toembryo research and human embryonic stem cell (hESC)research in Spain and the derivation of nine hESC lines atthe Center of Regenerative Medicine in Barcelona. You canfind the information for obtaining our lines for researchpurposes at blc@cmrb.eu.

Influence of "historic" photoperiod during stem elongation on the number of fertile florets in wheat

Extending the duration of the late reproductive phase in wheat has been proposed as a possible avenue to improve spike fertility. There is a positive correlation between the number of fertile florets and the duration of the stem elongation phase when this phase is varied by extended photoperiod. Photoperiod treatments imposed during the vegetative period also influence the duration of stem elongation. The present study analysed the effect of long photoperiod (19 h) of different duration (10, 12, 14, 18 or 22 d) imposed before the onset of stem elongation on floret fertility in wheat. It was found that the length of the stem elongation phase was modified by earlier ‘historic ’ photoperiod treatments imposed during previous phases. However, neither the number of fertile florets per spike nor the spikelet fertility was affected significantly by these historic treatments. The results of the study therefore showed that an increased duration of the late reproductive phase was ineffective in increasing the number of fertile florets, unless the length of that phase was directly altered by current photoperiod.

The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration

Planarian flatworms are an exception among bilaterians in that they possess a large pool of adult stem cells that enables them to promptly regenerate any part of their body, including the brain. Although known for two centuries for their remarkable regenerative capabilities, planarians have only recently emerged as an attractive model for studying regeneration and stem cell biology. This revival is due in part to the availability of a sequenced genome and the development of new technologies, such as RNA interference and next-generation sequencing, which facilitate studies of planarian regeneration at the molecular level. Here, we highlight why planarians are an exciting tool in the study of regeneration and its underlying stem cell biology in vivo, and discuss the potential promises and current limitations of this model organism for stem cell research and regenerative medicine.