1,721,278 research outputs found
Cell-replacement therapy with stem cells in neurodegenerative diseases
No full textIn the past few years, research on stem cells has expanded greatly as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several mechanisms such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation may explain positive therapeutic results, in addition to replacement of lost cells. The biological issue needs to be clarified in order to maximize the potential for effective therapies. The absence of any effective pharmacological treatment and preliminary data both in experimental and clinical settings has recently identified Amyotrophic Lateral Sclerosis (ALS) as an ideal candidate disease for the development of stem cell therapy in humans. Preliminary stem transplantation trials have already been performed in patients. The review discusses relevant topics regarding the application of stem cell research to ALS but in general to other neurodegenerative diseases debating in particular the issue of transdifferentiation, endogenous neural stem cell, and factors influencing the stem cell fate
A novel selective cell-permeable peptide disrupts presynaptic JNK2-STX1a interaction, providing neuroprotection and preventing glutamate-mediated excitotoxicity
Full text linkL-glutamate is the major excitatory neurotransmitter in the central nervous system of vertebrates. By playing a dual role as amino acid and neurotransmitter, glutamate fulfils a large array of physiological functions supporting neuronal development and cognitive performances. Consequently, the alteration of glutamate signaling entails profound detrimental effects that give rise to disease conditions, including excitotoxicity induced by cerebral ischemia.
Since plenty of reports have so far investigated the effects of cerebral ischemia at postsynaptic sites, little is known concerning the mechanisms activated by the ischemic injury at the presynaptic terminal.
NMDA receptors have been classically implicated in both postsynaptic and presynaptic pathways sustaining excitotoxicity, but only recently their intracellular association with the c-Jun N-terminal kinase (JNK) has also been involved in such pathological mechanisms.
Our previous findings already underlined a specific and unique involvement of the JNK2 isoform as a pivot player in glutamate release, when focusing on presynaptic sites. In the present dissertation we furthermore unveil the selective protein-protein interaction between JNK2 and Syntaxin-1a (STX1a), emphasizing their unexplored contribution in the docking and release of synaptic vesicles at the basis of the NMDA-evoked excitotoxicity. On purpose, we have developed JGRi1, a cell-permeable peptide able to selectively disrupt JNK2/STX1a interplay and pharmacologically prevent the downstream ischemic cascade. To uphold our hypothesis, we tested JGRi1 in several experimental settings, achieving a convincing neuroprotective effect also in a murine model of ischemia over a conveniently long therapeutic window. Conclusively, we analysed the presence of three single nucleotide polymorphisms (SNPs) on the STX1A gene in a cohort of stroke patients, evidencing a haplotype correlated with increased susceptibility to cerebral ischemia. Overall, we here confirm JNK fundamental implication in glutamate release at presynaptic level, moreover presenting for the first time JGRi1, a selective inhibitor of the JNK2/STX1a interaction that may represent a new therapeutic tool able to modulate glutamate overflow in various conditions, including neurodegenerative diseases and ischemia-linked pathologies
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
