Background: Hsp90 binding immunophilins may be regulators of the NF-B mechanism of action. Results: FKBP51 and FKBP52 show antagonistic properties on the nuclear accumulation and transcriptional activity of NF-B. Conclusion: Both immunophilins modulate NF-B trafficking and NF-B transcription when they are recruited to the promoter regions of target genes. Significance: The competitive effect between both immunophilins in different cell types may explain the pleiotropic actions of NF-B.

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Immunophilins are a family of intracellular receptors for immunosuppressive drugs. Those immunophilins that are related to immunosuppression are the smallest proteins of the family, i.e., FKBP12 and CyPA, whereas the other members of the family have higher molecular weight because the show additional domains to the drug-binding site. Among these extra domains, the TPR-domain is perhaps the most relevant because it permits the interaction of high molecular weight immunophilins with the 90-kDa heat-shock protein, Hsp90. This essential molecular chaperone regulates the biological function of several proteinkinases, oncogenes, protein phosphatases, transcription factors and cofactors . Hsp90-binding immunophilins where first characterized due to their association with steroid receptors. They regulate the cytoplasmic transport and the subcellular localization of these and other Hsp90 client proteins, as well as transcriptional activity, cell proliferation, cell differentiation and apoptosis. Hsp90-binding immunophilins are frequently overexpressed in several types of cancers and play a key role in cell survival. In this article we analyze the most important biological actions of the best characterized Hsp90-binding immunophilins in both steroid receptor function and cancer development and discuss the potential use of these immunophilins for therapeutic purposes as potential targets of specific small molecules.

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Pregnancy success requires a proper fetal maternal interaction at the establishment of implantation. Leptin has been described as a multitasking cytokine in pregnancy, particularly in the placenta, where it acts as an autocrine hormone. The expression of leptin in normal trophoblastic cells is regulated by different endogenous signals. We have previously reported that 17β-estradiol up-regulates placental leptin expression through genomic and non-genomic mechanisms. To improve the knowledge of estrogen receptor mechanisms in regulating leptin gene expression, we examined transcription nuclear factor kappa B (NFκB) effect on estradiol leptin induction in human BeWo cell line and human term placental explants. We demonstrated that estradiol induction effect on leptin expression is blocked by the inhibition of NFκB signaling. We also found that the overexpression of p65 subunit, the active form of NFκB, induces leptin expression. Moreover, the downregulation of estrogen receptor alpha (ERα through a specific siRNA, abolished NFκB effect on leptin expression. We also demonstrated that ERα enhanced NFκB signaling pathway activation in trophoblastic cells. Estradiol treatment significantly increased p65 expression and phosphorylation of the inhibitory protein κB alpha (IκBα). A reporter plasmid containing NFκB elements was also induced in response to estradiol stimulation. Localization experiments revealed that estradiol treatment induced nuclear localization of overexpressed p65. Moreover, the overexpression of ERα produced a complete displacement of p65 protein to the nucleus. Finally, immunoprecipitation experiments showed the presence of a complex containing ERαand NFκB. All these evidences suggest a cooperative behavior between ERαand NFκB transcription factors to induce leptin transcription.

The present geodetic reference frame in Latin America and the Caribbean is given by a network of about 400 continuously operating GNSS stations. These stations are routinely processed by ten Analysis Centres following the guidelines and standards set up by the International Earth Rotation and Reference Systems Service (IERS) and International GNSS Service (IGS). The Analysis Centres estimate daily and weekly station positions and station zenith tropospheric path delays (ZTD) with an hourly sampling rate. This contribution presents some attempts aiming at combining the individual ZTD estimations to generate consistent troposphere solutions over the entire region and to provide reliable time series of troposphere parameters, to be used as a reference. The study covers ZTD and IWV series for a time-span of 5 years (2014)(2015)(2016)(2017)(2018). In addition to the combination of the individual solutions, some advances based on the precise point positioning technique using BNC software (BKG NTRIP Client) and Bernese GNSS Software V.5.2 are presented. Results are validated using the IGS ZTD products and radiosonde IWV data. The agreement was evaluated in terms of mean bias and rms of the ZTD differences w.r.t IGS products (mean bias 1.5 mm and mean rms 6.8 mm) and w.r.t ZTD from radiosonde data (mean bias 2 mm and mean rms 7.5 mm). IWV differences w.r.t radiosonde IWV data (mean bias 0.41 kg/m 2 and mean rms 3.5 kg/m 2 ).

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