1,720,959 research outputs found
Carnosine modulates the Sp1-Slc31a1/Ctr1 copper-sensing system and influences copper homeostasis in murine CNS-derived cells
No full textCarnosine (CAR) is an endogenous dipeptide physiologically present in excitable tissues, such as central nervous system (CNS) and muscle. CAR is acknowledged as a substrate involved in many homeostatic pathways and mechanisms and, due to its biochemical properties, as a molecule intertwined with the homeostasis of heavy metals such as copper (Cu). In CNS, Cu excess and dysregulation imply oxidative stress, free-radical production, and functional impairment leading to neurodegeneration. Here, we report that CAR intercepts the regulatory routes of Cu homeostasis in nervous cells and tissues. Specifically, in a murine neuron-derived cell model, i.e., the B104 neuroblastoma cells, extracellular CAR exposure up to 24 h influenced intracellular Cu entry and affected (downregulated) the key Cu-sensing system, consisting of the gene coding for the Slc31a1 transmembrane Cu importer (alias Ctr1), and the gene coding for the Cu-responsive transcription factor Sp1 (Sp1). Also, CAR exposure upregulated CAR biosynthesis (Carns1), extracellular degradation (Cndp1), and transport (Slc15a4, alias Pht1) genes and elicited CAR intracellular accumulation, contributing to the outline of functional association between CAR and Cu within the cell. Interestingly, the same gene modulation scheme acting in vitro operates in vivo in brains of mice undergoing dietary administration of CAR in drinking water for 2 wk. Overall, our findings describe for the first time a regulatory interaction between CAR and Cu pathways in CNS and indicate CAR as a novel active molecule within the network of ligands and chaperones that physiologically regulate Cu homeostasis
Responsiveness of carnosine homeostasis genes in the pancreas and brain of streptozotocin-treated mice exposed to dietary carnosine
No full textIn excitable tissues, the endogenous dipeptide carnosine (CAR, β-Ala-l-His) sustains homeostatic responses to various challenges. By eliciting hypoglycemic effects via actions on the autonomic nervous system and protection of pancreatic beta-cells, CAR is also relevant in diabetes. We investigated the expression of genes involved in CAR biosynthesis, degradation, and membrane transport pathways, in the pancreas and brains of mice treated with streptozotocin (STZ) and then exposed to dietary CAR. We induced hyperglycemia by STZ intraperitoneal injections; then, STZ-treated mice received drinking water with or without CAR for two weeks. We report that CAR administration elicits beneficial effects on blood glucose levels and weight loss in STZ-treated mice and, remarkably, on the insulin gene products in the pancreas, preserving gene expression from STZ challenge. Also, we describe mRNA downregulation of the Slc15a2/Pept2 (dipeptide transporter) and Cndp2 (intracellular dipeptidase) genes in the pancreas of hyperglycemic mice, and dysregulation of Carns1 (CAR synthase), Pept2 and Cndp2 in brains; interestingly, dietary CAR elicits counteracting effects. These expression patterns associate with variations of CAR content in tissues of mice. Overall, our report suggests a direct role of CAR in the diabetes-affected pancreas and in the diabetes-targeted CNS, proposing (dys)regulation of CAR’s homeostasis as a marker conditio
The role of aberrant cell cycle events in Alzheimer’s disease: a study on a mouse model of AD and in a neuronal in vitro cell live system
Full text linkAlzheimer disease (AD) is the most common age related neurodegenerative disorder. The most frequent abnormalities found in Alzheimer’s disease (AD) brains are extracellular amyloid-b (Ab) plaques and intracellular neurofibrillary tangles (NFTs) that eventuate in neuronal cell death. The exact cellular events that drive these processes remain unclear, but neuropathological studies have previously linked neuronal death to the unexpected reappearance of cell cycle events. Over the past ten years, post-mortem studies in AD brains have reported re-expression of cell cycle related proteins in post-mitotic neurons. It is still unknown if these abnormalities in the cell cycle machinery potentially play an early, or even a causal role in the AD pathogenesis.
In this study, the APP23 mouse model of AD was used as a model to assess the ectopic cell cycling found in human AD by different histological methods. Results suggest that ectopic cell-cycle events in neurons are an early sign of neuronal dysfunction that occurs before deposition of Ab plaques and microglial inflammatory response. Furthermore, the co-expression of cyclins and apoptosis markers may be a contributing factor to the atrophy of the frontal cortex that was found in APP23 transgenic mice. These results support the hypothesis of a close association between neuronal death and expression of cell cycle related proteins in AD. More importantly however, they provide an outline of aberrant expression of different proteins of the cell cycle from young to old APP23 mice.
In the second part, a novel in vitro method was established that enabled the live- tracking of the cell cycle in primary hippocampal neurons using adeno-associated virus and cell live imaging. The results from the live imaging suggest that
abnormal progression/enter into the cell cycle of neurons might have protective roles in response to toxicity of oligomeric Ab species, indeed delaying and not determining the neuronal cell death, as thought to date. In summary, these data show that dysregulated ectopic re-activation of cell cycle-mediated events are associated with Ab pathology, in a mouse model of AD and in a new neuronal in vitro live system.
In addition to studying cell cycle in APP23 mice, a new immunotherapeutic treatment approach was tested in the TAU58 mouse model of frontotemporal dementia. These experiments showed a reduction of the histopathology and activation of the immune system in mice undergone active vaccination. This work may provide a new basis for future immunization studies in frontotemporal dementia
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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