El Liberalismo, la cristiandad y la historia de los prejuicios

Existe una infinidad de caminos para contar la(s) historia(s) de las sociedades y la política. Partiendo de ciertos conceptos tomados de Hannah Arendt, se ha trabajado sobre la posibilidad de hacer visible las mutaciones de los plexos de prejuicios sobre los que se sostienen ciertas transformaciones sociopolíticas de la historia occidental. Con el objetivo de estudiar las mutaciones prejuiciales y las configuraciones funcionales del sistema liberal, se llegó a plantear que con el nacimiento del liberalismo se habrían dado ciertas transformaciones en el entramado de prejuicios en las cuales la tradición cristiana cumplió un papel fundamental. El argumento apunta a que la transformación central sobre la que se cimentó el florecimiento del liberalismo habría tenido que ver con que los prejuicios morales de la herencia cristiana mutaron en su funcionalidad pasando a ocupar el lugar de los prejuicios políticos. En el presente texto se intentará, explicitar los fundamentos de esta perspectiva y a la vez mostrar tres puntos históricos del pensamiento sobre los cuales se puede hace visible el plante

Emx2 as a novel tool to suppress glioblastoma

Glioblastoma is a devastating CNS tumour for which no cure is presently available. We wondered if manipulation of Emx2, which normally antagonizes cortico-cerebral astrogenesis by inhibiting proliferation of astrocyte progenitors, may be employed to counteract it. We found that Emx2 overexpression induced the collapse of seven out of seven in vitro tested glioblastoma cell lines. Moreover, it suppressed four out of four of these lines in vivo. As proven by dedicated rescue assays, the antioncogenic activity of Emx2 originated from its impact on at least six metabolic nodes, which accounts for the robustness of its effect. Finally, in two out of two tested lines, the tumor culture collapse was also achieved when Emx2 was driven by a neural stem cell- specific promoter, likely active within tumor-initiating cells. All that points to Emx2 as a novel, promising tool for therapy of glioblastoma and prevention of its recurrencies

Cortico-cerebral histogenesis in the opossum Monodelphis domestica: generation of a hexalaminar neocortex in the absence of a basal proliferative compartment

<p>Abstract</p> <p>Background</p> <p>The metatherian <it>Monodelphis domestica</it>, commonly known as the South-American short-tailed opossum, is an appealing animal model for developmental studies on cortico-cerebral development. Given its phylogenetic position, it can help in tracing evolutionary origins of key traits peculiar to the eutherian central nervous system. The capability of its pup to regenerate damaged cortico-spinal connections makes it an ideal substrate for regenerative studies. Recent sequencing of its genome and the <it>ex utero </it>accessibility of its developing cerebral cortex further enhance its experimental interest. However, at the moment, a comprehensive cellular and molecular characterization of its cortical development is missing.</p> <p>Results</p> <p>A systematic analysis of opossum cortico-cerebral development was performed, including: origin of cortical neurons; migration of these neurons from their birthplaces to their final layer destinations; and molecular differentiation of distinct neocortical laminae.</p> <p>We observed that opossum projection neurons and interneurons are generated by pallial and subpallial precursors, respectively, similar to rodents. A six-layered cortex with a eutherian-like molecular profile is laid down, according to the inside-out rule. However, neocortical projection neurons are generated by apical neural precursors and almost no basal progenitors may be found in the neuronogenic neopallial primordium. In the opossum neocortex, <it>Tbr2</it>, the hallmark of eutherian basal progenitors, is transiently expressed by postmitotic progenies of apical precursors prior to the activation of more mature neuronal markers.</p> <p>Conclusions</p> <p>The neocortical developmental program predates Eutheria-Methatheria branching. However, in metatherians, unlike eutherians, a basal proliferative compartment is not needed for the formation of a six-layered neuronal blueprint.</p

Gamma-Ray Astrophysics

High-energy photons are a powerful probe for astrophysics and for fundamental physics in extreme conditions. During the recent years, our knowledge of the most violent phenomena in the Universe has impressively progressed thanks to the advent of new detectors for gamma rays, both at ground and on satellites. This article reviews the present status of high-energy gamma-ray astrophysics, with emphasis on the recent results and a look to the future.Comment: Accepted for publication on EPJ plu

Promotion of embryonic cortico-cerebral neuronogenesis by miR-124

Background: Glutamatergic neurons of the murine cerebral cortex are generated within periventricular proliferative layers of the embryonic pallium, directly from apical precursors or indirectly via their basal progenies. Cortical neuronogenesis is the result of different morphogenetic subroutines, including precursor proliferation and death, changes in histogenetic potencies, and post-mitotic neuronal differentiation. Control of these processes is extremely complex, involving numerous polypeptide-encoding genes. Moreover, many so-called 'non-coding genes' are also expressed in the developing cortex. Currently, their implication in corticogenesis is the subject of intensive functional studies. A subset of them encodes microRNAs (miRNAs), a class of small RNAs with complex biogenesis that regulate gene expression at multiple levels and modulate histogenetic progression and are implicated in refinement of positional information. Among the cortical miRNAs, miR-124 has been consistently shown to promote neuronogenesis progression in a variety of experimental contexts. Some aspects of its activity, however, are still controversial, and some have to be clarified. An in depth in vivo characterization of its function in the embryonic mammalian cortex is still missing. Results: By integrating locked nucleic acid (LNA)-oligo in situ hybridization, electroporation of stage-specific reporters and immunofluorescence, we reconstructed the cortico-cerebral miR-124 expression pattern during direct neuronogenesis from apical precursors and indirect neuronogenesis via basal progenitors. The miR-124 expression profile in the developing embryonic cortex includes an abrupt upregulation in apical precursors undergoing direct neuronogenesis as well as a two-step upregulation in basal progenitors during indirect neuronogenesis. Differential post-transcriptional processing seems to contribute to this pattern. Moreover, we investigated the role of miR-124 in embryonic corticogenesis by gain-of-function approaches, both in vitro, by lentivirus-based gene transfer, and in vivo, by in utero electroporation. Following overexpression of miR-124, both direct neuronogenesis and progression of neural precursors from the apical to the basal compartment were stimulated. Conclusion: We show that miR-124 expression is progressively up-regulated in the mouse embryonic neocortex during the apical to basal transition of neural precursor cells and upon their exit from cell cycle, and that miR-124 is involved in the fine regulation of these processes

Upregulating endogenous genes by an RNA-programmable artificial transactivator

To promote expression of endogenous genes ad libitum, we developed a novel, programmable transcription factor prototype. Kept together via an MS2 coat protein/RNA interface, it includes a fixed, polypeptidic transactivating domain and a variable RNA domain that recognizes the desired gene. Thanks to this device, we specifically upregulated five genes, in cell lines and primary cultures of murine pallial precursors. Gene upregulation was small, however sufficient to robustly inhibit neuronal differentiation. The transactivator interacted with target gene chromatin via its RNA cofactor. Its activity was restricted to cells in which the target gene is normally transcribed. Our device might be useful for specific applications. However for this purpose, it will require an improvement of its transactivation power as well as a better characterization of its target specificity and mechanism of action

Intraventricular Transplantation of Engineered Neuronal Precursors for In Vivo Neuroarchitecture Studies

Gene control of neuronal cytoarchitecture is currently the subject of intensive investigation. Described here is a simple method developed to study in vivo gene control of neocortical projection neuron morphology. This method is based on (1) in vitro lentiviral engineering of neuronal precursors as "test" and "control" cells, (2) their co-transplantation into wild-type brains, and (3) paired morphometric evaluation of their neuronal derivatives. Specifically, E12.5 pallial precursors from panneuronal, genetically labeled donors, are employed for this purpose. They are engineered to take advantage of selected promoters and tetON/OFF technology, and they are free-hand transplanted into neonatal lateral ventricles. Later, upon immunofluorescence profiling of recipient brains, silhouettes of transplanted neurons are fed into NeurphologyJ open source software, their morphometric parameters are extracted, and average length and branching index are calculated. Compared to other methods, this one offers three main advantages: it permits achieving of fine control of transgene expression at affordable costs, it only requires basic surgical skills, and it provides statistically reliable results upon analysis of a limited number of animals. Because of its design, however, it is not adequate to address non cell-autonomous control of neuroarchitecture. Moreover, it should be preferably used to investigate neurite morphology control after completion of neuronal migration. In its present formulation, this method is exquisitely tuned to investigate gene control of glutamatergic neocortical neuron architecture. Taking advantage of transgenic lines expressing EGFP in other specific neural cell types, it can be re-purposed to address gene control of their architecture

The Yin and Yang of nucleic acid-based therapy in the brain.

The post-genomic era has unveiled the existence of a large repertory of non-coding RNAs and repetitive elements that play a fundamental role in cellular homeostasis and dysfunction. These may represent unprecedented opportunities to modify gene expression at the right time in the correct space in vivo, providing an almost unlimited reservoir of new potential pharmacological agents. Hijacking their mode of actions, the druggable genome can be extended to regulatory RNAs and DNA elements in a scalable fashion. Here, we discuss the state-of-the–art of nucleic acid-based drugs to treat neurodegenerative diseases. Beneficial effects can be obtained by inhibiting (Yin) and increasing (Yang) gene expression, depending on the disease and the drug target. Together with the description of the current use of inhibitory RNAs (small inhibitory RNAs and antisense oligonucleotides) in animal models and clinical trials, we discuss the molecular basis and applications of new classes of activatory RNAs at transcriptional (RNAa) and translational (SINEUP) levels