Analysis of essential concepts and application in connection with setting up an enterprise, f.i. a “spin-­‐off”

This thesis is a compilation of the theoretical foundations of establishing a company and its application to the case of an academic “Spinc off”. Here, all the concepts regarding strategy and tools to develop it are touched. Also, there is a full analysis on the topic of university startc ups and their problems to grow. Next, a study of the current situation for universities and academic spinc offs in Eastern Germany is developed. Afterwards some good practices and recommendations for the case of Eastern German university spinc offs are listed.Departamento de Organización de Empresas y Comercialización e Investigación de MercadosGrado en Ingeniería en Organización Industria

Context, Entorn i Servei : l'aprenentatge mitjançant projectes, de les àrees científiques a la Interdisciplinarietat

El treball en contextos rellevants que proposa l'Aprenentatge Basat en Projectes, implica que, a més dels continguts científics, el projecte recluti continguts d'altres matèries. Aquesta interdisciplinarietat té una gestió complexa que, d'altra banda, permet projectes més connectats al món real. En aquest article, es descriuen 5 projectes de diferents àmbits de la ciència (astronomia, diversitat biològica, genètica, histologia) que s'han desenvolupat de forma interdisciplinària en funció de les necessitats i oportunitats didàctiques de diversoscontextos, incloent museus, criminologia, gestió d'espais urbans i col·laboració amb institucions externes.Project-Based Learning approaches in Science Education imply working in real contexts, and this need the work from several disciplines. The interdisciplinary approach is complex to develop but allows to construct projects with strong connections with the real world. In this article, we describe 5 projects from different science contents (astronomy, life diversity, genetics histology) that have been developed in a interdiscipinar frame following the needs and opportunities of several contexts, including museums, criminology, urban spaces administration and collaboration with other non-scholar institutions

Distribution of the transcription factor islet-1 in the central nervous system of nonteleost actinopterygian fish: Relationshipwith cholinergic and catecholaminergic systems

Islet-1 (Isl1) is one of the most conserved transcription factors in the evolution of vertebrates, due to its continuing involvement in such important functions as the differentiation of motoneurons, among other essential roles in cell fate in the forebrain. Although its functions are thought to be similar in all vertebrates, the knowledge about the conservation of its expression pattern in the central nervous system goes as far as teleosts, leaving the basal groups of actinopterygian fishes overlooked, despite their important phylogenetic position. In order to assess the extent of its conservation among vertebrates, we studied its expression pattern in the central nervous system of selected nonteleost actinopterygian fishes. By means of immunohistochemical techniques, we analyzed the Isl1 expression in the brain, spinal cord, and sensory ganglia of the cranial nerves of young adult specimens of the cladistian species Polypterus senegalus and Erpetoichthys calabaricus, the chondrostean Acipenser ruthenus, and the holostean Lepisosteus oculatus. We also detected the presence of the transcription factor Orthopedia and the enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) to better locate all the immunoreactive structures in the different brain areas and to reveal the possible coexpression with Isl1. Numerous conserved features in the expression pattern of Isl1 were observed in these groups of fishes, such as populations of cells in the subpallial nuclei, preoptic area, subparaventricular and tuberal hypothalamic regions, prethalamus, epiphysis, cranial motor nuclei and sensory ganglia of the cranial nerves, and the ventral horn of the spinal cord. Double labeling of TH and Isl1 was observed in cells of the preoptic area, the subparaventricular and tuberal hypothalamic regions, and the prethalamus, while virtually all motoneurons in the hindbrain and the spinal cord coexpressed ChAT and Isl1. Altogether, these results show the high degree of conservation of the expression pattern of the transcription factor Isl1, not only among fish, but in the subsequent evolution of vertebrates.Depto. de Biología CelularFac. de Ciencias BiológicasTRUEMinisterio de Ciencia e Innovación (MICINN)Universidad Complutense de Madrid (UCM)pu

Differential Estrogenic Effects of the Persistent Organochlorine Pesticides Dieldrin, Endosulfan, and Lindane in Primary Neuronal Cultures

The organochlorine chemicals endosulfan, dieldrin, and ghexachlorocyclohexane (lindane) are persistent pesticides to which people are exposed mainly via diet. Their antagonism of the g-aminobutyric acid-A (GABAA) receptor makes them convulsants. They are also endocrine disruptors because of their interaction with the estrogen receptor (ER). Here, we study the effects of dieldrin, endosulfan, and lindane on ERs in primary cultures of cortical neurons (CN) and cerebellar granule cells (CGC). All the compounds tested inhibited the binding of [3H]-estradiol to the ER in both CN and CGC, with dieldrin in CGC showing the highest affinity.We also determined the effects of the pesticides on protein kinase B (Akt) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation. Dieldrin and endosulfan increased Akt phosphorylation in CN, which was inhibited by the ERb antagonist 4-[2-phenyl-5,7- bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol. Instead, Akt and ERK1/2 phosphorylation induced by dieldrin in CGC was mediated by multiple activation of ERa, ERb, and G protein– coupled receptor 30. Lindane did not activate these pathways, but it inhibited estradiol-mediated Akt and ERK1/2 activation. In CN, all the chemicals activated ERK1/2 through a mechanism involving GABAA and glutamate receptors. Long-term exposure to these pesticides reduced the levels of ERa, but not of ERb. Moreover, extracts of CN treated with endosulfan, dieldrin, or lindane induced cell proliferation in MCF-7 human breast cancer–derived cells, whereas only extracts of CGC treated with dieldrin induced MCF-7 cell proliferation. Overall, the observed alterations on ER-mediated signaling and ER levels in neurons might contribute to the neurotoxicity of these organochlorine pesticides.Ministry of Health(FIS 061212, FIS 10/0453); CIBERESP (AA08-001); Generalitat de Catalunya (2009/SGR/214); Consejerı ´a de Innovacio´n, Ciencia y Empresa de la Junta de Andalucı´a (P09-CTS-5488).Peer reviewe

BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

NRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRAS(Q61)-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRAS(Q61) mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRAS(Q61)-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib. Targeted therapeutic options for NRAS-mutant melanoma are limited. Here, the authors show that under metabolic stress NRAS-mutant melanoma cells activate a BRAF-dependent glycolysis pathway for survival, leading to improve efficacy of sorafenib when combined with glycolysis inhibitors

Evaluación de la actividad docente en el desarrollo de competencias profesionales

Memoria ID-0130. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Could Duodenal Molecular Mechanisms be Involved in the Hypocholesterolemic Effect of Silicon Used as Functional Ingredient in Late‐Stage Type 2 Diabetes Mellitus?

Scope: Hypercholesterolemia increases the risk of mortality in type 2 diabetesmellitus (T2DM), especially in the late-stage. Consumption of bioactivecompounds as functional ingredients would help achieve therapeutic goals forcholesterolemia. Silicon has demonstrated a hypocholesterolemic effect andthe ability to reduce fat digestion. However, it is unclear whether silicon exertssuch effect in late-stage T2DM (LD) and the intestinal mechanisms involved.Methods and results: Three groups of eight rats were included: early-stageT2DM control (ED), LD, and the LD group treated with silicon (LD-Si) oncethe rats were diabetic. Morphological alterations of the duodenal mucosa, andlevels of markers involve in cholesterol absorption and excretion, besidecholesterolemia, and fecal excretion were assayed. Silicon included as afunctional ingredient significantly reduces cholesterolemia in part due to: 1)reducing cholesterol intestinal absorption by decreasing the absorptive areaand Acetyl-Coenzyme A acetyltransferase-2 (ACAT2) levels; and 2) increasingcholesterol excretion to the lumen by induction of the liver X receptor (LXR)and consequent increase of adenosine triphosphate-binding cassettetransporter (ABCG5/8).Conclusions: These results provide insight into the intestinal molecularmechanisms by which silicon reduces cholesterolemia and highlights theefficacy of the consumption of silicon-enriched functional foods in late-stageT2DM

The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: The case of the spike A222V mutation

The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has since reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness