50 research outputs found

    Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17β-HSD type 4

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    <p>Abstract</p> <p>Background</p> <p>Steroids affect many tissues, including the brain. In the zebra finch, the estrogenic steroid estradiol (E<sub>2</sub>) is especially effective at promoting growth of the neural circuit specialized for song. In this species, only the males sing and they have a much larger and more interconnected song circuit than females. Thus, it was surprising that the gene for 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4), an enzyme that converts E<sub>2 </sub>to a less potent estrogen, had been mapped to the Z sex chromosome. As a consequence, it was likely that HSD17B4 was differentially expressed in males (ZZ) and females (ZW) because dosage compensation of Z chromosome genes is incomplete in birds. If a higher abundance of HSD17B4 mRNA in males than females was translated into functional enzyme in the brain, then contrary to expectation, males could produce less E<sub>2 </sub>in their brains than females.</p> <p>Results</p> <p>Here, we used molecular and biochemical techniques to confirm the HSD17B4 Z chromosome location in the zebra finch and to determine that HSD17B4 mRNA and activity were detectable in the early developing and adult brain. As expected, HSD17B4 mRNA expression levels were higher in males compared to females. This provides further evidence of the incomplete Z chromosome inactivation mechanisms in birds. We detected HSD17B4 mRNA in regions that suggested a role for this enzyme in the early organization and adult function of song nuclei. We did not, however, detect significant sex differences in HSD17B4 activity levels in the adult brain.</p> <p>Conclusions</p> <p>Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E<sub>2 </sub>metabolizing enzyme, but that dosage compensation of this Z-linked gene may occur via post-transcriptional mechanisms.</p

    Is Evolution of Blind Mole Rats Determined by Climate Oscillations?

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    The concept of climate variability facilitating adaptive radiation supported by the ‘‘Court Jester’’ hypothesis is disputed by the ‘‘Red Queen’’ one, but the prevalence of one or the other might be scale-dependent. We report on a detailed, comprehensive phylo-geographic study on the ,4 kb mtDNA sequence in underground blind mole rats of the family Spalacidae (or subfamily Spalacinae) from the East Mediterranean steppes. Our study aimed at testing the presence of periodicities in branching patterns on a constructed phylogenetic tree and at searching for congruence between branching events, tectonic history and paleoclimates. In contrast to the strong support for the majority of the branching events on the tree, the absence of support in a few instances indicates that network-like evolution could exist in spalacids. In our tree, robust support was given, in concordance with paleontological data, for the separation of spalacids from muroid rodents during the first half of the Miocene when open, grass-dominated habitats were established. Marine barriers formed between Anatolia and the Balkans could have facilitated the separation of the lineage ‘‘Spalax’’ from the lineage ‘‘Nannospalax’’ and of the clade ‘‘leucodon’’ from the clade ‘‘xanthodon’’. The separation of the clade ‘‘ehrenbergi’’ occurred during the late stages of the tectonically induced uplift of the Anatolian high plateaus and mountains, whereas the separation of the clade ‘‘vasvarii’’ took place when the rapidly uplifting Taurus mountain range prevented the Mediterranean rainfalls from reaching the Central Anatolian Plateau. The separation of Spalax antiquus and S. graecus occurred when the southeastern Carpathians were uplifted. Despite the role played by tectonic events, branching events that show periodicity corresponding to 400-kyr and 100-kyr eccentricity bands illuminate the important role of orbital fluctuations on adaptive radiation in spalacids. At the given scale, our results supports the ‘‘Court Jester’’ hypothesis over the ‘‘Red Queen’’ one

    Estrogen Receptor β-Selective Agonists Stimulate Calcium Oscillations in Human and Mouse Embryonic Stem Cell-Derived Neurons

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    Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER) in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERα and ERβ on calcium oscillations in neurons derived from human (hES) and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERβ, but not ERα. The non-selective ER agonist 17β-estradiol (E2) rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERα agonist 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT). In contrast, the selective ERβ agonists, 2,3-bis(4-Hydroxyphenyl)-propionitrile (DPN), MF101, and 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041) stimulated calcium oscillations similar to E2. The ERβ agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERβ activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERβ signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds

    Status and Plans for the National Spherical Torus Experimental Research Facility

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    “Just listen to us”: The Role of Teacher Empowerment in the Implementation of Responsiveness to Intervention

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    This is the Page Proof version of the following article Pyle, A., Wade-Woolley, L., & Hutchinson, N. L. (2011). “Just listen to us”: The Role of Teacher Empowerment in the Implementation of Responsiveness to Intervention. Alberta Journal of Educational Research, 57(3), 258-272 which has been published in final form at www.ajer.ca, self- archived with permission from the Alberta Journal of Educational ResearchTeachers play a vital role in the implementation of new programs. This article discusses how best to support teachers in the face of such change. Specifically, we describe the perspectives of teachers who participated in a pilot project of the responsiveness to intervention model. Through focus group data, the researchers explored the barriers that they have encountered during the first year of implementation. Despite these supports, one major barrier persisted: all the participants in this study described feelings of powerlessness. This article explores the roots of these frustrations and the resulting role of teacher empowerment in the successful implementation of new programs. Teachers play a crucial role in the implementation of the new programs. This article discusses ways to support teachers with this kind of change. More specifically, we describe the perspectives of teachers who participated in a pilot project on the intervention responsiveness model. Drawing on data from focus groups, the researchers examined both the barriers teachers face in the first year of implementation and the supports that helped them overcome some of these barriers. Despite these supports, an important barrier remained: all the participants in this study described a feeling of helplessness
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