Characterization of the 5' upstream regulatory region of the human myostatin gene: regulation of myostatin gene transcription by dexamethasone in vitro

We cloned and characterized a 3.3-kb fragment containing the 5'-regulatory region of the human myostatin gene. The promoter sequence contains putative muscle growth response elements for glucocorticoid, androgen, thyroid hormone, myogenic differentiation factor 1, myocyte enhancer factor 2, peroxisome proliferator-activated receptor, and nuclear factor-kappaB. To identify sites important for myostatin's gene transcription and regulation, eight deletion constructs were placed in C(2)C(12) and L6 skeletal muscle cells. Transcriptional activity of the constructs was found to be significantly higher in myotubes compared with that of myoblasts. To investigate whether glucocorticoids regulate myostatin gene expression, we incubated both cell lines with dexamethasone. On both occasions, dexamethasone dose dependently increased both the promoter's transcriptional activity and the endogenous myostatin expression. The effects of dexamethasone were blocked when the cells were coincubated with the glucocorticoid receptor antagonist RU-486. These findings suggest that glucocorticoids upregulate myostatin expression by inducing gene transcription, possibly through a glucocorticoid receptor-mediated pathway. We speculate that glucocorticoid-associated muscle atrophy might be due in part to the upregulation of myostatin expression.

Cytohesin Binder and Regulator (Cybr) is Not Essential for T- and Dendritic-Cell Activation and Differentiation

Cybr (also known as Cytip, CASP, and PSCDBP) is an interleukin-12-induced gene expressed exclusively in hematopoietic cells and tissues that associates with Arf guanine nucleotide exchange factors known as cytohesins. Cybr levels are dynamically regulated during T-cell development in the thymus and upon activation of peripheral T cells. In addition, Cybr is induced in activated dendritic cells and has been reported to regulate dendritic cell (DC)-T-cell adhesion. Here we report the generation and characterization of Cybr-deficient mice. Despite the selective expression in hematopoietic cells, there was no intrinsic defect in T- or B-cell development or function in Cybr-deficient mice. The adoptive transfer of Cybr-deficient DCs showed that they migrated efficiently and stimulated proliferation and cytokine production by T cells in vivo. However, competitive stem cell repopulation experiments showed a defect in the abilities of Cybr-deficient T cells to develop in the presence of wild-type precursors. These data suggest that Cybr is not absolutely required for hematopoietic cell development or function, but stem cells lacking Cybr are at a developmental disadvantage compared to wild-type cells. Collectively, these data demonstrate that despite its selective expression in hematopoietic cells, the role of Cybr is limited or largely redundant. Previous in vitro studies using overexpression or short interfering RNA inhibition of the levels of Cybr protein appear to have overestimated its immunological role.

The SuperWASP wide-field exoplanetary transit survey: candidates from fields 23 h <RA <03 h

Photometric transit surveys promise to complement the currently known sample of extra-solar planets (ESPs) by providing additional information on the planets and especially their radii. Here, we present ESP candidates from one such survey called, the Wide Angle Search for Planets (WASP) obtained with the SuperWASP wide-field imaging system. Observations were taken with SuperWASP North located in La Palma during the 2004 April to October observing season. The data cover fields between 23 and 03 h in RA at declinations above +12. This amounts to over ~400000 stars with V magnitudes 8-13.5. For the stars brighter than 12.5, we achieve better than 1 per cent photometric precision. Here, we present 41 sources with low-amplitude variability between ~1 and 10 mmag, from which we select 12 with periods between 1.2 and 4.4 d as the most promising ESP candidates. We discuss the properties of these ESP candidates, the expected fraction of transits recovered for our sample and implications for the frequency and detection of hot-Jupiters.

Mutations affecting the Rossman fold of isoleucyl-tRNA synthetase are correlated with low-level mupirocin resistance in Staphylococcus aureus.

The isoleucyl-tRNA synthetase (ileS) gene was sequenced in toto from 9 and in part from 31 Staphylococcus aureus strains with various degrees of susceptibility to mupirocin. All strains for which the mupirocin MIC was greater than 8 µg/ml contained point mutations affecting the Rossman fold via Val-to-Phe changes at either residue 588 (V588F) or residue 631 (V631F). The importance of the V588F mutation was confirmed by an allele-specific PCR survey of 32 additional strains. Additional mutations of uncertain significance were found in residues clustered on the surface of the IleS protein.

The IHS monogram as a symbol of Catholic resistance in 17th century Ireland

It has been suggested that the presence of religious images and scenes in secular buildings of sixteenth-century date can be viewed as an expression of resistance by the native Irish to English colonial activity in the aftermath of the Munster Plantation (J. A. Delle, 1999, International Journal of Historical Archaeology 3: 11–35). Such images, however, may merely represent a continuation into the early modern period of a Medieval tradition of adorning secular houses with devotional images. If a religious symbol of native Catholic resistance to English colonization and Protestantism in Munster is to be sought then perhaps a more appropriate image would be the I.H.S. monogram—a symbol associated with the Counter Reformation and the Jesuits. The paper presents an example of the monogram located within a tower house at Gortnetubbrid in County Limerick, Ireland.