1,720,972 research outputs found
Protective effect of glutathione on damage induced by permethrin in a neuronal model of PC12 cells.
No full textObjective: Permethrin, a member of the family of synthetic pyrethroids, can induce oxidative stress and impairment in expression of Nurr1, a transcription factor essential for the maintenance of dopaminergic neurons. These conditions, flanked to low level of glutathione (GSH), are typical in neurons affected by Parkinson Disease (PD). The aim of this study is to evaluate in vitro effects of GSH on a stress dependent parameters (Nurr1) measured in PC12 cells culture treated with permethrin.
Methods: PC12 cells were seeded and treated for 72h with 1uM permethrin and separately co-treated with the pesticide and 32nM glutathione (1). Then, qRT-PCR was performed to evaluate Nurr1 gene expression.
Results: In cells cultures under stress condition, such as those induced by permethrin, Nurr1 gene expression changed, maybe as a compensatory effect to damage. In contrast, when cells were co-treated with glutathione, Nurr1 value was reestablished as the control.
Conclusion: Pesticides, mainly assumed with diet, can modulate gene expression leading to the onset and progression of age-related diseases. Permethrin, in particular, can induce stress in neuronal dopaminergic cells, mimicking PD condition (2). As demonstrated by previous in vivo studies, permethrin exposure can lead to progressive neuronal damage characterized by GSH and Nurr1 deficit (3,4). The present study shows that GSH in vitro can contrast the negative effect induced by permethrin. We can hypothesize that GSH can prevent oxidative stress damage, avoiding cells to overreact by modifying the production of Nurr1. Hence, GSH can act as a preventive agent to cellular damage induced by permethrin.
References
1. Mesner PW, Winters TR, Green SH. (1992). Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons. J Cell Biol 119:1669–1680.
2. Carloni, M., Nasuti, C., Fedeli, D., Montani. M., Amici, A., Vadhana, M.S.D., Gabbianelli, R., 2013. Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2, Brain Research 1515, 19-28.
3. Falcioni ML, Nasuti C, Bergamini C, Fato R, Lenaz G. ( 2010). The primary role of GSH against nuclear DNA damage of striatum induced by permethrin in rats. Neuroscience 168(1), 2-10.
4. Nasuti C, Falcioni ML, Nwankwo IE, Cantalamessa F, Gabbianelli R. (2008). Effect of permethrin plus antioxidants on locomotor activity and striatum in adolescent rats. Toxicology., 29;251(1-3):45-50
The dual face of parathyroid hormone and prostaglandins in the osteoimmune system.
No full textThe microenvironment of bone marrow, an extraordinarily heterogeneous and dynamic system, is populated by bone and immune cells, and its functional dimension has been at the forefront of recent studies in the field of osteoimmunology. The interaction of both marrow niches supports self-renewal, differentiation, and homing of the hematopoietic stem cells and provides the essential regulatory molecules for osteoblast and osteoclast homeostasis. Impaired signaling within the niches results in a pathological tableau and enhances disease, including osteoporosis and arthritis, or the rejection of hematopoietic stem cell transplants. Discovering the anabolic players that control these mechanisms has become warranted. In this review, we focus on parathyroid hormone (PTH) and prostaglandins (PGs), potent molecular mediators, both of which carry out a multitude of functions, particularly in bone lining cells and T cells. These two regulators proved to be promising therapeutic agents when strictly clinical protocols on dose treatments were applied
Disruptors of sestrin-MAPK interactions rejuvenate T cells and expand TCR specificity
No full textWhereas treatments that reactivate exhausted T cells are available, strategies to rejuvenate terminally differentiated senescent lymphocytes are yet to be developed. Senescent T cells, with short telomeres and inactive telomerase, are different from exhausted cells, and may form due to defective telomere transfer reactions upon contact with antigen presenting cells (APCs). Senescent T cells are characterized by presence of sestrin-MAPK kinase activation complexes (sMACs), large immune-inhibitory protein assemblies of sestrins bound to a stress/energy sensing kinase (AMPK) and three functional effector kinases (ERK, JNK and p38 MAPKs). Here we described first in class Disruptors of the Sestrin-MAPK immune-inhibitory Complex (DOS), which target sMAC to ubiquitin-dependent proteasomal degradation, resulting in long-term sestrin transcriptional inhibition, increased T cell fitness, and generation of long-lived stem like memory features. Strikingly, the DOS generated stem T cells present de novo antigen-specific T-cell receptor DNA rearrangements that precede their future expansion. Although largely senescent at the point of treatment, the DOS regenerated T cells, with stem features and new TCRs, initiated immune-protective rejuvenation-dependent responses to new challenges, with or without vaccination. Therefore, it is possible to generate new T cell clones from formerly senescent cells and expand immune specificit
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
- …
