1,720,963 research outputs found
Rb-Dependent Regulation of Adult Neurogenesis in the Aging Brain Along the Subventricular Zone – Olfactory Bulb Axis
Get PDFCell cycle machinery is at the center of maintaining the adult neural stem/progenitor cells (NSPCs) throughout life at the two neurogenic sites: the subgranular zone (SGZ) of the hippocampus, and the subventricular zone (SVZ) whose newborn neurons migrate into the olfactory bulb (OB). The Retinoblastoma protein, Rb, is a critical cell cycle protein which was previously implicated in maintaining neurogenesis in the embryonic and young adult brain. In addition, it was associated with the crucial task of preventing/controlling cell cycle re-entry (CCE) in postmitotic neurons, a process whose failure is indicative of early signs of neurodegeneration. However, the role of Rb in maintaining neurogenesis in the aged brain is still undefined. Here, we study the short-term and long-term effects of an Rb inducible knockout (Rb iKO) mouse model, specifically along the SVZ-OB axis in the mid-aged and old-aged brain. We rely on our established model of NestinCreERT2/Rosa26YFP/Rbflox mice to induce the loss of Rb in a time-dependent manner, through tamoxifen-induced Cre/loxP activation in Nestin-positive brain cells in young and aged mice (Nestin is an intermediate filament known to be expressed in adult NSPCs). We will first address the efficiency of the NestinCreERT2 model in mid-aged (MA, 12-14 months old) and old-aged (OA, 20 months old) brain tissues of mice sacrificed at 28 days post-tamoxifen administration (28dpt), by assessing Cre mRNA expression (through in situ hybridization) together with YFP and Nestin protein expression (by double immunohistochemistry, IHC). Second, we will look at the effect of Rb iKO on NSPC proliferation and neuronal commitment in MA and OA brain tissues, each of mice sacrificed at 28dpt and 60dpt. In addition, we will address neuronal migration along the rostral migratory stream (RMS) and later maturation in the OB in Rb+/- and Rb-/- mice at these timepoints. Finally, we will address CCE and DNA damage profiles in the young-aged (YA)-28dpt and MA-210dpt OB tissues following Rb iKO, along with markers of early neurodegenerative protein aggregations.
We first report a near-complete overlap in Cre mRNA and YFP protein expression in the MA-28dpt and OA-28dpt SVZ, together with a high co-expression of YFP and Nestin in SVZ NSPCs at these timepoints. This indicates that Cre recombination is efficient in our line of choice. Next, we observe no significant variation in co-expression of SVZ YFP with Ki67 (a proliferation marker), DCX (early commitment/differentiation marker), Sox2 (a late stem/early progenitor marker), and pH3 (a late mitotic marker) in Rb+/- and Rb-/- mice at MA-28dpt, MA-60dpt, OA-28dpt and OA-60dpt. Along the RMS, however, we report an impaired neuronal migration following Rb iKO in MA-28dpt, which translates into a significant decline in OB neurogenesis at this timepoint. We then show evidence of incomplete CCE (YFP co-IHC with PCNA, Ki67 and pH3) and DNA damage (YFP co-IHC with γH2A.X) in adult-born OB neurons in Rb-/- mice compared to matching controls at YA-28dpt, but not at MA-210dpt or YA-480dpt. Last, we did not observe an abnormal expression of neurotoxic species (tau and α-synuclein) in the OB at MA-210dpt and YA-480dpt following Rb iKO. In conclusion, we establish the NestinCreERT2 transgenic line as an efficient tool to study acute KO effect in the mid-aged and old-aged mouse brain. We also identify a distinct requirement for Rb during adult neurogenesis in the MA and OA SVZ-OB axis in contrast to the YA brain. Moreover, we emphasize the critical role of Rb in maintaining survival of newborn adult neurons by preventing CCE and accumulation of DNA damage. As a result, this study emphasizes the non-monotonic changes in gene regulation of adult neurogenesis with age, thereby highlighting the limitations and potential of implicating this process in neurorehabilitation and neurodegeneration alike
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
Role of the retinoblastoma protein (Rb) in the survival and function of adult-born neurons in the olfactory bulb -
No full textThesis. M.S. American University of Beirut. Department of Biology, 2016. T:6376Advisor : Dr. Noël Ghanem, Assistant Professor, Biology ; Members of Committee : Dr. Sawsan Kreydiyyeh, Professor, Biology ; Dr. Arne Dietrich, Professor, Psychology.Includes bibliographical references (leaves 50-59)The olfactory bulb (OB) is one of two neurogenic regions where ongoing replacement of neurons occurs throughout life in the adult mammalian brain. Adult-born interneurons are thus continuously generated from adult neural stem cells (aNSCs) found in the subventricular zone (SVZ) lining the lateral ventricles. Neuronal progenitors proliferate and migrate along the rostral migratory stream (RMS) to the OB where they integrate into the olfactory circuit. In a recent study, we have established a role for the Retinoblastoma protein (Rb) in the control of the rate of adult neurogenesis and showed that conditional deletion of Rb in NSCs-progenitors results in enhanced neurogenesis in the SVZ-OB one month later. However, this amplified production of immature neurons was only transient and gradually declined thereafter to match control levels by 120 days post-deletion of Rb, which suggested a further requirement for Rb in the long-term survival of newborn neurons. In this study, we have assessed the latter hypothesis using two distinct Nestin-CreERT2-YFP transgenic mice lines, Rbflox-flox mice and retroviral-mediated Cre delivery in order to delete Rb in the adult SVZ-NSCs. We subsequently performed histological analyses and birthdating studies using the cell death marker active-caspase 3 (AC-3) and the thymidine analog bromodeoxyuridine (BrdU), respectively. As a result, we detected a massive increase in cell death inside the OB that peaked around 60 days post-Rb deletion in Nestin-CreERT2 mice and this was true in the viral studies but more prominent at 28d. Given that the OB is essential for processing olfactory information, we examined the functional significance of enhanced neurogenesis one month following the loss of Rb. We found a positive correlation between the integration of excess adult-born neurons and the performance of mice in difficult olfactory tasks such as associative learning based on odor-discrimination between similar odors but not dissimilar odors. Altogether, our data demonstrate a critical require
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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