1,721,161 research outputs found
Protein aggregation and defective RNA metabolism as mechanisms for motor neuron damage
No full textThe presence of protein inclusions within the central nervous system is a characteristic of most neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Aggregates may induce cell death trough several mechanisms, such as sequestration of essential cellular components, clogging of the proteasome system, and/or disruption of axonal transport. The neuropathological signature of ALS is represented by the presence of ubiquitinated inclusions immunoreactive for the protein TDP-43 in the cytoplasm of motor neurons. Recent studies demonstrated that a significant percentage of familial ALS cases are caused by pathogenic mutations in the TAR DNA binding protein and fused in sarcoma/translocated in liposarcoma genes encoding, respectively, for TDP-43 and FUS proteins. Both TDP-43 and FUS are DNA/RNA-binding proteins involved in transcriptional regulation and splicing, shuttling, maturation and transport of mRNA molecules. Mutations in the two genes seem to induce a nucleo-cytoplasmic redistribution of FUS and TDP-43, possibly promoting aggregate formation and/or disrupting their physiological nuclear functions or their interactions with specific RNA targets. Those findings collectively suggest that alterations in cellular RNA metabolism may trigger motor neuron degeneration
La diagnosi di Sclerosi Laterale Amiotrofica(SLA): 2009
No full textThe diagnosis of ALS per se may be challenging since there is no single diagnostic test for the disease with the exception, today, of finding a mutation in defined genes as SOD1, TDP-43, etc. The World Federation of Neurology (WFN) developed workable, internationally acceptable diagnostic criteria that would enhance clinical and research studies in the field of ALS. The revised El Escorial criteria edited in 2000 (Brooks et al., 2000) state that to establish the diagnosis of ALS, a combination of LMN and UMN signs with evidence of spread is required. Four cardinal regions have been defined and spread of signs from region to region is essential for the character of ALS. On clinical ground it is seldom possible to establish an early diagnosis of ALS that needs then to be supported mainly by neurophysiological testing. In clinical practice the differential diagnosis of ALS is extensive because symptoms and signs of both LMN and UMN are encountered in a large and varied group of disorders, both neurologic and systemic. Furthermore, today two areas deserve particular attention in the process of diagnosis: cognitive impairments once considered rare or uncommon occur in a large percentage of ALS patients. Careful neuropsychological testing needs indeed to be completed for possible overlapping forms with fronto-temporal dementia (FTDL). Furthermore, the most intriguing area is related to genetics. Since 1993 and the definition of SOD1 mutations in familial ALS, other genes have been discovered and the impact of genetics on ALS diagnosis is today critical. An accurate understanding of the familial contribution to ALS would have a significant impact on the diagnosis of individuals both at an early age, prior to the onset of symptoms or at the first appearance of symptoms. In practice, the diagnosis of any is made by a process of clinic logic that is defined both by the characteristics of the disease itself and by an intuitive process of decision making in which the clinician weights the clinical evidence according to an experiential model built from clinical experience gained over time. In ALS, this concept must be revisited because the recent impact of new genetic discoveries requires to the clinician a continuous update for the genotype-clinical phenotype coupling. New genetic acquisitions can unquestionably speed early diagnosis of ALS
Stem cells in Amyotrophic Lateral Sclerosis: motor neuron protection or replacement?
No full textGiven the lack of effective drug treatments for amyotrophic lateral sclerosis (ALS), compelling preclinical data on stem cell research has targeted this disease as a candidate for stem cell treatment. Stem cell transplantation has been effective in several animal models, but the underlying biological pathways of restorative processes are still unresolved. Several mechanisms such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation may explain positive therapeutic results in pre-clinical animal models, in addition to replacement of lost motor neurons. The clinical target in ALS has shifted from being neuron-centered to focus on the interaction between motor neurons and non-neuronal cells (mainly astroglial or microglial). In fact, one of the fundamental unanswered questions in ALS is whether and how much motor neuron death depends on neighboring cells, and how wild-type non-neuronal cells may protect motor neurons expressing an ALS-causing mutation. Lately, motor neuron replacement has been successfully achieved in animal models with reinnervation of the muscle target. Even if many biological issues need to be solved in pre-clinical models, preliminary stem cell transplantation trials have been performed in ALS patients with conflicting results. The review discusses relevant topics regarding the application of stem cell research to ALS focusing on their therapeutic relevance and mechanisms of action
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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