196,093 research outputs found
Cellule staminali di osteosarcoma umano 3AB-OS: un modello per analizzare le proprietà oncogeniche di p53 mutata.
No full textAlterazioni del gene TP53 si riscontrano in circa il 50% dei tumori umani (1). Negli ultimi anni è stato
dimostrato che la proteina mutata p53 (mp53) acquisisce nuove proprietà oncogeniche, definite “gain of
function” (GOF), che contribuiscono alla progressione tumorale (2). In questo studio è stato analizzato lo
stato del gene TP53, della proteina da esso espressa e il loro ruolo nella promozione della proliferazione,
invasività, resistenza all’apoptosi e staminalità delle cellule 3AB-OS, una linea tumorale staminale
precedentemente isolata dalle cellule di osteosarcoma umano MG63 (3). Analisi comparative di RT-PCR,
Methylation-Specific-PCR (MSP), Fluorescent-in situ-hybridization (FISH) e sequenziamento hanno
evidenziato che, nelle cellule 3AB-OS, il gene TP53 è mutato, presenta un promotore non metilato, è
espresso ad elevati livelli ed è presente in copie multiple che non sempre co-localizzano con il cromosoma
17 (dove normalmente è localizzato il gene TP53). Nelle cellule parentali MG63, invece, non è possibile
apprezzare livelli misurabili di espressione del gene TP53, che è presente in singola copia, non co-localizza
con il cromosoma 17 ed è caratterizzato da un promotore metilato. Inoltre, analisi di western-blot e
immunofluorescenza per mp53, hanno dimostrato che nelle cellule 3AB-OS essa risulta espressa, stabilizzata
da modifiche post-traduzionali (fosforilazione/acetilazione) e localizzata esclusivamente nel nucleo. Per
valutare l’acquisizione di proprietà oncogeniche da parte di mp53, sono stati condotti studi di silenziamento
genico transiente, mediante l’utilizzo di small-interfering-RNA. Il knockdown di mp53 induce un’evidente
riduzione della proliferazione cellulare e dell’invasività assieme a un incremento della sensibilità
all’induttore di morte TRAIL. Analisi di Real-Time-PCR e di Western-Blot condotte su geni e relative
proteine implicati nella cancerogenesi e nella staminalità, mostrano risultati congrui con i dati precedenti.
Complessivamente, questi studi dimostrano che nelle cellule 3AB-OS la proteina endogena mp53 svolge un
ruolo oncogenico, suggerendo che tali cellule possano rappresentare un valido modello sperimentale per la
comprensione sia dei meccanismi molecolari attraverso cui mp53 esplica le sue attività oncogeniche che del
suo ruolo nell’iniziazione del cancro
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Oxidative Damage and Antioxidant Response in Frontal Cortex of Demented and Nondemented Individuals with Alzheimer's Neuropathology
No full textAlzheimer's disease (AD) is characterized by progressive neurodegeneration in the cerebral cortex, histopathologically hallmarked by amyloid β (Aβ) extracellular plaques and intracellular neurofibrillary tangles, constituted by hyperphosphorylated tau protein. Correlation between these pathologic features and dementia has been challenged by the emergence of "nondemented with Alzheimer's neuropathology" (NDAN) individuals, cognitively intact despite displaying pathologic features of AD. The existence of these subjects suggests that some unknown mechanisms are triggered to resist Aβ-mediated detrimental events. Aβ accumulation affects mitochondrial redox balance, increasing oxidative stress status, which in turn is proposed as a primary culprit in AD pathogenesis. To clarify the relationship linking Aβ, oxidative stress, and cognitive impairment, we performed a comparative study on AD, NDAN, and aged-matched human postmortem frontal cortices of either sex. We quantitatively analyzed immunofluorescence distribution of oxidative damage markers, and of SOD2 (superoxide dismutase 2), PGC1α [peroxisome proliferator-activated receptor (PPAR) γ-coactivator 1α], PPARα, and catalase as key factors in antioxidant response, as well as the expression of miRNA-485, as a PGC1α upstream regulator. Our results confirm dramatic redox imbalance, associated with impaired antioxidant defenses in AD brain. By contrast, NDAN individuals display low oxidative damage, which is associated with high levels of scavenging systems, possibly resulting from a lack of PGC1α miRNA-485-related inhibition. Comparative analyses in neurons and astrocytes further highlighted cell-specific mechanisms to counteract redox imbalance. Overall, our data emphasize the importance of transcriptional and post-transcriptional regulation of antioxidant response in AD. This suggests that an efficient PGC1α-dependent "safety mechanism" may prevent Aβ-mediated oxidative stress, supporting neuroprotective therapies aimed at ameliorating defects in antioxidant response pathways in AD patients
Haematopoietic stem cell transplantation in poor prognosis MDS and sAML: prolonged patients survival is achievable, but refining of infections management and reduction of treatment-related toxicities is required to improve patients outcome
No full textDispelling the Myths Behind First-author Citation Counts
No full textWe 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
Dr. Glendon Swarthout
No full textHosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness
Immunomodulatory drugs in the context of autologous hematopoietic stem cell transplantation associate with reduced pro-tumor t cell subsets in multiple myeloma
No full textImmunomodulatory drugs (IMiDs) are effective therapeutics for multiple myeloma (MM), where in different clinical settings they exert their function both directly on MM cells and indirectly by modulating immune cell subsets, although with not completely defined mechanisms. Here we studied the role of IMiDs in the context of autologous hematopoietic stem cell transplantation on the T cell subset distribution in the bone marrow of newly diagnosed MM patients. We found that after transplantation pro-tumor Th17-Th1 and Th22 cells and their related cytokines were lower in patients treated with IMiDs during induction chemotherapy compared to untreated patients. Of note, lower levels of IL-17, IL-22, and related IL-6, TNF-α, IL-1β, and IL-23 in the bone marrow sera correlated with treatment with IMiDs and favorable clinical outcome. Collectively, our results suggest a novel anti-inflammatory role for IMiDs in MM
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