8 resultados para 1459
Resumo:
The AINT/ERIC/TACC genes encode novel proteins with a coiled coil domain at their C-terminus. The founding member of this expanding family of genes, transforming acidic coiled coil 1 (TACC1), was isolated from a BAC contig spanning the breast cancer amplicon-1 on 8p11. Transfection of cells in vitro with TACC1 resulted in anchorage-independent growth consistent with a more "neoplastic" phenotype. Database searches employing the human TACC1 sequence revealed other novel genes, TACC2 and TACC3, with substantial sequence homology particularly in the C-terminal regions encoding the coiled coil domains. TACC2, located at 10q26, is similar to anti-zuai-1 (AZU-1), a candidate breast tumour suppressor gene, and ECTACC, an endothelial cell TACC which is upregulated by erythropoietin (Epo). The murine homologue of TACC3, murine erythropoietin-induced cDNA (mERIC-1) was also found to be upregulated by Epo in the Friend virus anaemia (FVA) model by differential display-PCR. Human ERIC-1, located at 4p16.3, has been cloned and encodes an 838-amino acid protein whose N- and C-terminal regions are highly homologous to the shorter 558-amino acid murine protein, mERIC-1. In contrast, the central portions of these proteins differ markedly. The murine protein contains four 24 amino acid imperfect repeats. ARNT interacting protein (AINT), a protein expressed during embryonic development in the mouse, binds through its coiled coil region to the aryl hydrocarbon nuclear translocator protein (ARNT) and has a central portion that contains seven of the 24 amino acid repeats found in mERIC-1. Thus mERIC-1 and AINT appear to be developmentally regulated alternative transcripts of the gene. Most members of the TACC family discovered so far contain a novel nine amino acid putative phosphorylation site with the pattern [R/K]-X(3)-[E]-X(3)-Y. Genes with sequence homology to the AINT/ERIC/TACC family in other species include maskin in Xenopus, D-TACC in Drosophila and TACC4 in the rabbit. Maskin contains a peptide sequence conserved among eIF-4E binding proteins that is involved in oocyte development. D-TACC cooperates with another conserved microtubule-associated protein Msps to stabilise spindle poles during cell division. The diversity of function already attributed to this protein family, including both transforming and tumour suppressor properties, should ensure that a new and interesting narrative is about to unfold.
Resumo:
Optical and near-infrared (near-IR) observations of the Type Ic supernova (SN Ic) 2004aw are presented, obtained from -3 to +413 d with respect to the B-band maximum. The photometric evolution is characterized by a comparatively slow post-maximum decline of the light curves. The peaks in redder bands are significantly delayed relative to the bluer bands, the I-band maximum occurring 8.4 d later than that in B. With an absolute peak magnitude of -18.02 in the V band the SN can be considered fairly bright, but not exceptional. This also holds for the U through I bolometric light curve, where SN 2004aw has a position intermediate between SNe 2002ap and 1998bw. Spectroscopically SN 2004aw provides a link between a normal SN Ic like SN 1994I and the group of broad-lined SNe Ic. The spectral evolution is rather slow, with a spectrum at day +64 being still predominantly photospheric. The shape of the nebular [O-I] lambda lambda 6300, 6364 line indicates a highly aspherical explosion. Helium cannot be unambiguously identified in the spectra, even in the near-IR. Using an analytical description of the light-curve peak we find that the total mass of the ejecta in SN 2004aw is 3.5-8.0 M-circle dot, significantly larger than that in SN 1994I, although not as large as in SN 1998bw. The same model suggests that about 0.3 M-circle dot of Ni-56 has been synthesized in the explosion. No connection to a GRB can be firmly established.
Resumo:
Many international business (IB) studies have used foreign direct investment (FDI) stocks to measure the aggregate value-adding activity of multinational enterprises (MNE) affiliates in host countries. We argue that FDI stocks are a biased measure of that activity, because the degree to which they overestimate or underestimate affiliate activity varies systematically with host-country characteristics. First, most FDI into countries that serve as tax havens generate no actual productive activity; thus FDI stocks in such countries overestimate affiliate activity. Second, FDI stocks do not include locally raised external funds, funds widely used in countries with well-developed financial markets or volatile exchange rates, resulting in an underestimation of affiliate activity in such countries. Finally, the extent to which FDI translates into affiliate activity increases with affiliate labor productivity, so in countries where labor is more productive, FDI stocks also result in an underestimation of affiliate activity. We test these hypotheses by first regressing affiliate value-added and affiliate sales on FDI stocks to calculate a country-specific mismatch, and then by regressing this mismatch on a host country's tax haven status, level of financial market development, exchange rate volatility, and affiliate labor productivity. All hypotheses are supported, implying that FDI stocks are a biased measure of MNE affiliate activity, and hence that the results of FDI-data-based studies of such activity need to be reconsidered. [ABSTRACT FROM AUTHOR]
Resumo:
Aims: Myocardial ischemia/reperfusion (I/R) is associated with mitochondrial dysfunction and subsequent cardiomyocyte death. The generation of excessive quantities of reactive oxygen species (ROS) and resultant damage to mitochondrial enzymes is considered an important mechanism underlying reperfusion injury. Mitochondrial complex I can exist in two interconvertible states: active (A) and deactive or dormant (D). We have studied the active/deactive (A/D) equilibrium in several tissues under ischemic conditions in vivo and investigated the sensitivity of both forms of the heart enzyme to ROS.
Results: We found that in the heart, t½ of complex I deactivation during ischemia was 10?min, and that reperfusion resulted in the return of A/D equilibrium to its initial level. The rate of superoxide generation by complex I was higher in ischemic samples where content of the D-form was higher. Only the D-form was susceptible to inhibition by H2O2 or superoxide, whereas turnover-dependent activation of the enzyme resulted in formation of the A-form, which was much less sensitive to ROS. The mitochondrial-encoded subunit ND3, most likely responsible for the sensitivity of the D-form to ROS, was identified by redox difference gel electrophoresis.
Innovation: A combined in vivo and biochemical approach suggests that sensitivity of the mitochondrial system to ROS during myocardial I/R can be significantly affected by the conformational state of complex I, which may therefore represent a new therapeutic target in this setting.
Conclusion: The presented data suggest that transition of complex I into the D-form in the absence of oxygen may represent a key event in promoting cardiac injury during I/R.
Resumo:
The ~16-ka-long record of explosive eruptions from Shiveluch volcano (Kamchatka, NW Pacific) is refined using geochemical fingerprinting of tephra and radiocarbon ages. Volcanic glass from 77 prominent Holocene tephras and four Late Glacial tephra packages was analyzed by electron microprobe. Eruption ages were estimated using 113 radiocarbon dates for proximal tephra sequence. These radiocarbon dates were combined with 76 dates for regional Kamchatka marker tephra layers into a single Bayesian framework taking into account the stratigraphic ordering within and between the sites. As a result, we report ~1,700 high-quality glass analyses from Late Glacial–Holocene Shiveluch eruptions of known ages. These define the magmatic evolution of the volcano and provide a reference for correlations with distal fall deposits. Shiveluch tephras represent two major types of magmas, which have been feeding the volcano during the Late Glacial–Holocene time: Baidarny basaltic andesites and Young Shiveluch andesites. Baidarny tephras erupted mostly during the Late Glacial time (~16–12.8 ka BP) but persisted into the Holocene as subordinate admixture to the prevailing Young Shiveluch andesitic tephras (~12.7 ka BP–present). Baidarny basaltic andesite tephras have trachyandesite and trachydacite (SiO2 < 71.5 wt%) glasses. The Young Shiveluch andesite tephras have rhyolitic glasses (SiO2 > 71.5 wt%). Strongly calc-alkaline medium-K characteristics of Shiveluch volcanic glasses along with moderate Cl, CaO and low P2O5 contents permit reliable discrimination of Shiveluch tephras from the majority of other large Holocene tephras of Kamchatka. The Young Shiveluch glasses exhibit wave-like variations in SiO2 contents through time that may reflect alternating periods of high and low frequency/volume of magma supply to deep magma reservoirs beneath the volcano. The compositional variability of Shiveluch glass allows geochemical fingerprinting of individual Shiveluch tephra layers which along with age estimates facilitates their use as a dating tool in paleovolcanological, paleoseismological, paleoenvironmental and archeological studies. Electronic tables accompanying this work offer a tool for statistical correlation of unknown tephras with proximal Shiveluch units taking into account sectors of actual tephra dispersal, eruption size and expected age. Several examples illustrate the effectiveness of the new database. The data are used to assign a few previously enigmatic wide-spread tephras to particular Shiveluch eruptions. Our finding of Shiveluch tephras in sediment cores in the Bering Sea at a distance of ~600 km from the source permits re-assessment of the maximum dispersal distances for Shiveluch tephras and provides links between terrestrial and marine paleoenvironmental records.