BAG3 (Bcl-2 associated athanogene 3)

Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that interacts with the ATPase domain of the heat shock protein (Hsp) 70 through BAG domain. BAG3 is induced by stressful stimuli, mainly through the activity of heat shock factor 1 on bag3 gene promoter.In addition to the BAG domain, BAG3 contains also a WW domain and a proline-rich (PXXP) repeat, that mediate binding to partners different from Hsp70.These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. BAG3 is expressed also in several tumor types where it sustains cell survival, resistance to therapy, and/or motility and metastatization (Rosati et al., 2011)

BAG3 (Bcl-2 associated athanogene 3)

Review on BAG3 (Bcl-2 associated athanogene 3), with data on DNA, on the protein encoded, and where the gene is implicated

Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic leukemia cells by NFkB/Rel- specific decoy oligodeoxynucleotides

The activity of NF-kB/Rel nuclear factors is known to inhibit apoptosis in various cell types. We investigated whether the subtraction of NF-kB/Rel activity influenced the response of 11 AML (M1, M2 and M4) patients’ cells to AraC. To this end we used a phosphorothioate double-stranded decoy oligodeoxynucleotide (ODN) carrying the NF-kB/Rel- consensus sequence. Cell incubation with this ODN, but not its mutated (scrambled) form used as a control, resulted in abating the NF-kB/Rel nuclear levels in these cells, as verified by electrophoretic mobility shift assay (EMSA) of cells’ nuclear extracts. We incubated the leukemic cells with AraC (32 or 1 mM), in either the absence or presence of the decoy or the scrambled ODN, and analyzed cell apoptosis. The spontaneous cell apoptosis detectable in the absence of AraC (,25%) was not modulated by the oligonucleotide presence in cell cultures. On the other hand, in 10 of the 11 samples tested, the decoy kB, but not the scrambled ODN significantly (P ,0.01 in a Student’s t test) enhanced cell apoptotic response to AraC. Such an effect was particularly remarkable at low AraC doses (1 mM). These findings indicate that NF-kB/Rel activity influences response to AraC in human primary myeloblastic cells, and suggests that the inhibition of NF-kB/Rel factors can improve the effect of chemotherapy in AM

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

Retinoic acid reduces human neuroblastoma cell migration and invasiveness: effects on DCX, LIS1, neurofilaments-68 and vimentin expression

<p>Abstract</p> <p>Background</p> <p>Neuroblastoma is a severe pediatric tumor, histologically characterised by a variety of cellular phenotypes. One of the pharmacological approaches to neuroblastoma is the treatment with retinoic acid. The mechanism of action of retinoic acid is still unclear, and the development of resistance to this differentiating agent is a great therapy problem.</p> <p>Doublecortin, a microtubule-associated protein involved in neuronal migration, has recently been proposed as a molecular marker for the detection of minimal residual disease in human neuroblastoma. Nevertheless, no information is available on the expression of doublecortin in the different cell-types composing human neuroblastoma, its correlation with neuroblastoma cell motility and invasiveness, and the possible modulations exerted by retinoic acid treatment.</p> <p>Methods</p> <p>We analysed by immunofluorescence and by Western blot analysis the presence of doublecortin, lissencephaly-1 (another protein involved in neuronal migration) and of two intermediate filaments proteins, vimentin and neurofilament-68, in SK-N-SH human neuroblastoma cell line both in control conditions and under retinoic acid treatment. Migration and cell invasiveness studies were performed by wound scratch test and a modified microchemotaxis assay, respectively.</p> <p>Results</p> <p>Doublecortin is expressed in two cell subtypes considered to be the more aggressive and that show high migration capability and invasiveness.</p> <p>Vimentin expression is excluded by these cells, while lissencephaly-1 and neurofilaments-68 are immunodetected in all the cell subtypes of the SK-N-SH cell line. Treatment with retinoic acid reduces cell migration and invasiveness, down regulates doublecortin and lissencephaly-1 expression and up regulates neurofilament-68 expression. However, some cells that escape from retinoic acid action maintain migration capability and invasiveness and express doublecortin.</p> <p>Conclusion</p> <p>a) Doublecortin is expressed in human neuroblastoma cells that show high motility and invasiveness;</p> <p>b) Retinoic acid treatment reduces migration and invasiveness of the more aggressive cell components of SK-N-SH cells;</p> <p>c) The cells that after retinoic acid exposure show migration and invasive capability may be identified on the basis of doublecortin expression.</p

Efficacies of the new Paclitaxel-eluting Coroflex Please™ Stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Please™ and Taxus™ (ECO-PLEASANT) trial: study rationale and design

<p>Abstract</p> <p>Background</p> <p>Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Please™ stent is a newly developed drug eluting stent using the Coroflex™ stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Please™ stent were within the range of those of Taxus, the 1^stgeneration paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Please™ stent with the Taxus Liberte™ stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Please™ stent compared with Taxus Liberte™ stent in a head-to-head manner.</p> <p>Methods</p> <p>In the comparison of Efficacy between COroflex PLEASe™ ANd Taxus™ stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please™ stent and Taxus Liberte™ stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.</p> <p>Discussion</p> <p>The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please™ versus Taxus Liberte™ stent. On the basis of this trial, we will be able to find out whether the Coroflex Please™ stent is non-inferior to Taxus Liberte™ stent or not.</p> <p>Trial registration</p> <p>ClinicalTrials.gov number, NCT00699543.</p

Translational Control through eIF2alpha Phosphorylation during the Leishmania Differentiation Process

The parasitic protozoan Leishmania alternates between an invertebrate and a mammalian host. Upon their entry to mammalian macrophages, Leishmania promastigotes differentiate into amastigote forms within the harsh environment of the phagolysosomal compartment. Here, we provide evidence for the importance of translational control during the Leishmania differentiation process. We find that exposure of promastigotes to a combined elevated temperature and acidic pH stress, a key signal triggering amastigote differentiation, leads to a marked decrease in global translation initiation, which is associated with eIF2α phosphorylation. Interestingly, we show that amastigotes adapted to grow in a cell-free medium exhibit lower levels of protein synthesis in comparison to promastigotes, suggesting that amastigotes have to enter a slow growth state to adapt to the stressful conditions encountered inside macrophages. Reconversion of amastigotes back to promastigote growth results in upregulation of global translation and a decrease in eIF2α phosphorylation. In addition, we show that while general translation is reduced during amastigote differentiation, translation of amastigote-specific transcripts such as A2 is preferentially upregulated. We find that A2 developmental gene regulation is triggered by temperature changes in the environment and that occurs mainly at the level of translation. Upon elevated temperature, the A2 transcript is stabilized through its association with polyribosomes leading to high levels of translation. When temperature decreases during amastigote to promastigote differentiation, the A2 transcript is not longer associated with translating polyribosomes and is being gradually degraded. Overall, these findings contribute to our better understanding of the adaptive responses of Leishmania to stress during its development and highlight the importance of translational control in promastigote to amastigote differentiation and vice-versa

Embryonic Diapause Is Conserved across Mammals

Embryonic diapause (ED) is a temporary arrest of embryo development and is characterized by delayed implantation in the uterus. ED occurs in blastocysts of less than 2% of mammalian species, including the mouse (Mus musculus). If ED were an evolutionarily conserved phenomenon, then it should be inducible in blastocysts of normally non-diapausing mammals, such as domestic species. To prove this hypothesis, we examined whether blastocysts from domestic sheep (Ovis aries) could enter into diapause following their transfer into mouse uteri in which diapause conditions were induced. Sheep blastocysts entered into diapause, as demonstrated by growth arrest, viability maintenance and their ED-specific pattern of gene expression. Seven days after transfer, diapausing ovine blastocysts were able to resume growth in vitro and, after transfer to surrogate ewe recipients, to develop into normal lambs. The finding that non-diapausing ovine embryos can enter into diapause implies that this phenomenon is phylogenetically conserved and not secondarily acquired by embryos of diapausing species. Our study questions the current model of independent evolution of ED in different mammalian orders

Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons

In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies