186,596 research outputs found
Mitochondrial glutamate carrier GC1 as a newly identified player in the control of glucose-stimulated insulin secretion
No full textThe SLC25 carrier family mediates solute transport across the inner mitochondrial membrane, a process that is still poorly characterized regarding both the mechanisms and proteins implicated. This study investigated mitochondrial glutamate carrier GC1 in insulin-secreting β-cells. GC1 was cloned from insulin-secreting cells, and sequence analysis revealed hydropathy profile of a six-transmembrane protein, characteristic of mitochondrial solute carriers. GC1 was found to be expressed at the mRNA and protein levels in INS-1E β-cells and pancreatic rat islets. Immunohistochemistry showed that GC1 was present in mitochondria, and ultrastructural analysis by electron microscopy revealed inner mitochondrial membrane localization of the transporter. Silencing of GC1 in INS-1E β-cells, mediated by adenoviral delivery of short hairpin RNA, reduced mitochondrial glutamate transport by 48% (p < 0.001). Insulin secretion at basal 2.5mM glucose and stimulated either by intermediate 7.5 mM glucose or non-nutrient 30 mM KCl was not modified by GC1 silencing. Conversely, insulin secretion stimulated with optimal 15 mM glucose was reduced by 23% (p < 0.005) in GC1 knocked down cells compared with controls. Adjunct of cell-permeant glutamate (5mM dimethyl glutamate) fully restored the secretory response at 15 mM glucose (p < 0.005). Kinetics of insulin secretion were investigated in perifused isolated rat islets. GC1 silencing in islets inhibited the secretory response induced by 16.7 mM glucose, both during first (-25%, p<0.05) and second (-33%, p<0.05) phases. This study demonstrates that insulin-secreting cells depend on GC1 for maximal glucose response, thereby assigning a physiological function to this newly identified mitochondrial glutamate carrier. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc
Reading acts of narrative appropriation: four instances of fraudulent memoir
No full textPhDThis thesis examines acts of narrative appropriation, the telling of purportedly‘authentic’ life stories by those for whom the stories are not theirs to tell. This
misuse or subversion of genre - the discipline of historical writing and the category
of autobiography - becomes a means for cultural, social and political dissimulation,
and the analysis focuses both on the act: the event, trespass, or ‘theft’ of another’s
life story, and on the cultural meaning that this event reveals. These narrative acts
are approached theoretically through discussions of what it means to be an author, a
reader, and through the consideration of literary and social genre, category and form.
In exploring identities at particular risk of appropriation, this thesis shows how
fraudulent appropriated narratives affect our reading of the world, and in turn
influence our perception of already marginalized social groups. My primary
examples include prostitution ‘narratives’, Native North American ‘memoir,’ and
fraudulent Holocaust survivor ‘testimony,’ with each text providing decoded
evidence of ‘genre-bending’ exhibiting a social and political intent. These works
seek to be read as authentic personal narratives, as autobiography, and that is how
they have been presented to the reader. However, they are imposters – fictional tales
desiring the elevated status of historical authenticity and willing to bend the rules
and contracts of genre to achieve their end. Here the appearance of authenticity is
achieved through the use of cultural and social ‘myth,’ or perceptions of cultural
identity, and as such its fraudulent construction is first and foremost a social act,
with a social and economic motivation. As this thesis concludes, these texts are
most successful when their own political and social ideologies echo and confirm that
of the readership; when their subjects, the fraudulent ‘I’ at the center of the text is
also a performative elaboration of cultural belief
Changes in mitochondrial carriers exhibit stress-Specific signatures in INS-1E ß-cells exposed to glucose versus fatty acids
No full textChronic exposure of ß-cells to metabolic stresses impairs their function and potentially induces apoptosis. Mitochondria play a central role in coupling glucose metabolism to insulin secretion. However, little is known on mitochondrial responses to specific stresses; i.e. low versus high glucose,saturated versus unsaturated fatty acids, or oxidative stress. INS-1E cells were exposed for 3 days to 5.6 mM glucose, 25 mM glucose, 0.4 mM palmitate, and 0.4 mM oleate. Culture at standard 11.1 mM glucose served as no-stress control and transient oxidative stress (200 μM H2O2 for 10 min at day 0) served as positive stressful condition. Mito-array analyzed transcripts of 60
mitochondrion-associated genes with special focus on members of the Slc25 family. Transcripts of interest were evaluated at the protein level by immunoblotting. Bioinformatics analyzed the
expression profiles to delineate comprehensive networks. Chronic exposure to the different metabolic stresses impaired glucose-stimulated insulin secretion; revealing glucotoxicity and
lipo-dysfunction. Both saturated and unsaturated fatty acids increased expression of the
carnitine/acylcarnitine carrier CAC, whereas the citrate carrier CIC and energy sensor SIRT1 were
specifically upregulated by palmitate and oleate, respectively. High glucose upregulated CIC, the
dicarboxylate carrier DIC and glutamate carrier GC1. Conversely, it reduced expression of energy
sensors (AMPK, SIRT1, SIRT4), metabolic genes,transcription factor PDX1, and anti-apoptotic Bcl2.
This was associated with caspase-3 cleavage and cell death. Expression levels of GC1 and SIRT4 exhibited positive and negative glucose dose-response, respectively. Expression profiles of energy
sensors and mitochondrial carriers were selectively modified by the different conditions, exhibiting
stress-specific signatures
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Loss of prohibitin induces mitochondrial damages altering ss-cell function and survival and responsible for gradual diabetes development.
No full textProhibitins are highly conserved proteins mainly implicated in the maintenance of mitochondrial function and architecture. Their dysfunctions are associated with aging, cancer, obesity, and inflammation. However, their possible role in pancreatic beta-cells remains unknown. The current study documents the expression of prohibitins in human and rodent islets and their key role for beta-cell function and survival. Ablation of Phb2 in mouse beta-cells sequentially resulted in impairment of mitochondrial function and insulin secretion, loss of beta-cells, progressive alteration of glucose homeostasis, and, ultimately, severe diabetes. Remarkably, these events progressed over a 3-week period of time after weaning. Defective insulin supply in beta-Phb2(-/-) mice was contributed by both beta-cell dysfunction and apoptosis, temporarily compensated by increased beta-cell proliferation. At the molecular level, we observed that deletion of Phb2 caused mitochondrial abnormalities, including reduction of mitochondrial DNA copy number and respiratory chain complex IV levels, altered mitochondrial activity, cleavage of L-optic atrophy 1, and mitochondrial fragmentation. Overall, our data demonstrate that Phb2 is essential for metabolic activation of mitochondria and, as a consequence, for function and survival of beta-cells
Metabolomics identifies a biomarker revealing in vivo loss of functional β-cell mass before diabetes onset
No full textIdentification of individuals with decreased functional β-cell mass is essential for the prevention of diabetes. However, in vivo detection of early asymptomatic β-cell defect remains unsuccessful. Metabolomics has emerged as a powerful tool in providing readouts of early disease states before clinical manifestation. We aimed at identifying novel plasma biomarkers for loss of functional β-cell mass in the asymptomatic prediabetes stage. Nontargeted and targeted metabolomics were applied in both lean β-Phb2-/- (β-cell-specific prohibitin-2 knockout) mice and obese db/db (leptin receptor mutant) mice, two distinct mouse models requiring neither chemical nor dietary treatments to induce spontaneous decline of functional β-cell mass promoting progressive diabetes development. Nontargeted metabolomics on β-Phb2-/- mice identified 48 and 82 significantly affected metabolites in liver and plasma, respectively. Machine learning analysis pointed to deoxyhexose sugars consistently reduced at the asymptomatic prediabetes stage, including in db/db mice, showing strong correlation with the gradual loss of β-cells. Further targeted metabolomics by gas chromatography-mass spectrometry uncovered the identity of the deoxyhexose, with 1,5-anhydroglucitol displaying the most substantial changes. In conclusion, this study identified 1,5-anhydroglucitol as associated with the loss of functional β-cell mass and uncovered metabolic similarities between liver and plasma, providing insights into the systemic effects caused by early decline in β-cells
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe 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
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
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