1,720,989 research outputs found
Differential regulation of multiple glucose transporter genes in Leishmania mexicana
We have studied the structure and expression of glucose transporter genes in the parasitic protozoan Leishmania mexicana. Three distinct glucose transporter isoforms, LmGT1, LmGT2, and LmGT3, are encoded by single copy genes that are clustered together at a single locus. Quantitation of Northern blots reveals thatLmGT2 mRNA is present at ∼15-fold higher level in promastigotes, the insect stage of the parasite life cycle, compared with amastigotes, the intracellular stage of the life cycle that lives within the mammalian host. In contrast, LmGT1 andLmGT3 mRNAs are expressed at similar levels in both life cycle stages. Transcription of the LmGT genes in promastigotes and axenically cultured amastigotes occurs at similar levels, as measured by nuclear run-on transcription. Consequently, the ∼15-fold up-regulation of LmGT2 mRNA levels in promastigotes compared with amastigotes must be controlled at the post-transcriptional level. Measurement of LmGT2 RNA decay in promastigotes and axenic amastigotes treated with actinomycin D suggests that differential mRNA stability may play a role in regulating glucose transporter mRNA levels in the two life cycle stages
Strategies to dissect parasite proteomes
<p>Proteomes are complex and dynamic entities that are still poorly understood, but the application of proteomic technologies has become invaluable in many areas of biology, including parasitology. These technologies can be exploited to identify proteins in both complex or relatively simple samples, that formerly could only be characterized by targeted approaches such as Western blotting. Quantitative proteomic approaches can reveal modulations in protein expression that accompany phenotypes of interest. Proteomic approaches have been exploited to understand some of the molecular basis for host:parasite interactions and to elucidate phenotypes such as virulence, antigenicity and drug resistance. Many of the same technologies can also be more easily applied to targeted sub-proteomes.</p>
<p>Examples from several studies on pathogen proteomes and sub-proteomes, from bacteria to helminths, are presented to illustrate the potential and limitations of proteomic technologies.</p>
Neuroproteomics
Neuroscience is a broad research area, which traditionally has roots in anatomy and biology but which extends into areas as diverse as computer science and philosophy. Since the brain was first implicated as the seat of consciousness, scientists have sought to understand brain function and dysfunction. The complex anatomy of the nervous system has been studied in detail and the role of specific structures has been implicated in many processes and pathologies. However the mechanisms by which the nervous system functions to process information are rather poorly understood. As populations age, the impact of neurological abnormality or malfunction becomes ever more significant and the impetus to understand the brain is heightened. Proteomics has a clear potential to contribute to our understanding of the molecular mechanisms that underpin brain function. 'Neuroproteomics', edited by Oscar Alzate, encapsulates some of the key areas in which proteomic technologies are making an impact in neuroscience
Glucose transport in amastigotes and promastigotes of Leishmania mexicana mexicana
Promastigotes and amastigotes of Leishmania mexicana mexicana transported 2-deoxy-d-glucose (2-DOG) by a saturable process with a Km of 24 ± 3 μM and Vmax of 2.21 nmol min−1 (mg protein)−1 for the promastigote and a Km of 29 ± 8 μM and Vmax of 0.13 nmol min−1 (mg protein)−1 for the amastigote stage. Amastigotes incorporated 2-DOG maximally at pH 5.0, while for promastigotes the optimum was at pH 7.0. Mid-log phase promastigotes were found to accumulate 2-DOG via a stereospecific carrier-mediated process which was competitively inhibited by d-glucose and d-mannose but not l-glucose. Transport was dependent upon temperature, with a Q10 in promastigotes of 1.83 and an optimum rate at 35°C (±4°C) with an activation energy of 50.12 kJ mol−1. Stationary phase promastigotes accumulated 2-DOG at approximately twice the rate of mid-log phase promastigotes. Cytochalasin B, forskolin and phloretin were all found to inhibit human erythrocyte 2-DOG uptake but only cytochalasin B was found significantly to inhibit promastigote 2-DOG uptake. Interestingly, leishmanial 2-DOG uptake was inhibited by a series of membrane potential antagonists including the ionophore monensin, the H+ATPase inhibitor N,N′-dicyclohexylcarbodiimide (DCCD) and uncoupling agent carbonylcyanide-4-(triflouromethoxy) phenylhydrazone (FCCP), as well as, the tricyclic drugs chlomipramine and imipramine, but was insensitive to the Na+/K+ ATPase inhibitor ouabain and the antitrypanosomal drugs Pentostam and Suramin. We therefore conclude that there are significant structural and mechanistic differences between the d-glucose uptake systems of Leishmania and the mammalian host to merit the inclusion of glucose transporters as putative targets for rational drug design
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
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