| 1. |
- Cruz-Gallardo, I., et al.
(författare)
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The binding of TIA-1 to RNA C-rich sequences is driven by its C-terminal RRM domain
- 2014
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Ingår i: Rna Biology. - : Informa UK Limited. - 1547-6286 .- 1555-8584. ; 11:6, s. 766-776
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Tidskriftsartikel (refereegranskat)abstract
- T-cell intracellular antigen-1 (TIA-1) is a key DNA/RNA binding protein that regulates translation by sequestering target mRNAs in stress granules (SG) in response to stress conditions. TIA-1 possesses three RNA recognition motifs (RRM) along with a glutamine-rich domain, with the central domains (RRM2 and RRM3) acting as RNA binding platforms. While the RRM2 domain, which displays high affinity for U-rich RNA sequences, is primarily responsible for interaction with RNA, the contribution of RRM3 to bind RNA as well as the target RNA sequences that it binds preferentially are still unknown. Here we combined nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) techniques to elucidate the sequence specificity of TIA-1 RRM3. With a novel approach using saturation transfer difference NMR (STD-NMR) to quantify protein-nucleic acids interactions, we demonstrate that isolated RRM3 binds to both C-and U-rich stretches with micromolar affinity. In combination with RRM2 and in the context of full-length TIA-1, RRM3 significantly enhanced the binding to RNA, particularly to cytosine-rich RNA oligos, as assessed by biotinylated RNA pull-down analysis. Our findings provide new insight into the role of RRM3 in regulating TIA-1 binding to C-rich stretches, that are abundant at the 5' TOPs (5' terminal oligopyrimidine tracts) of mRNAs whose translation is repressed under stress situations.
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| 2. |
- Perez, R. V., et al.
(författare)
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Investigating fusion plasma instabilities in the Mega Amp Spherical Tokamak using mega electron volt proton emissions
- 2014
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 85:11, s. 11D701-
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Tidskriftsartikel (refereegranskat)abstract
- The proton detector (PD) measures 3 MeV proton yield distributions from deuterium-deuterium fusion reactions within the Mega Amp Spherical Tokamak (MAST). The PD's compact four-channel system of collimated and individually oriented silicon detectors probes different regions of the plasma, detecting protons (with gyro radii large enough to be unconfined) leaving the plasma on curved trajectories during neutral beam injection. From first PD data obtained during plasma operation in 2013, proton production rates (up to several hundred kHz and 1 ms time resolution) during sawtooth events were compared to the corresponding MAST neutron camera data. Fitted proton emission profiles in the poloidal plane demonstrate the capabilities of this new system.
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| 3. |
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| 4. |
- O'Leary, Patrick C., et al.
(författare)
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Peroxiredoxin-1 protects estrogen receptor alpha from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer
- 2014
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 16:4, s. R79-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Peroxiredoxin-1 (PRDX1) is a multifunctional protein, acting as a hydrogen peroxide (H2O2) scavenger, molecular chaperone and immune modulator. Although differential PRDX1 expression has been described in many tumors, the potential role of PRDX1 in breast cancer remains highly ambiguous. Using a comprehensive antibody-based proteomics approach, we interrogated PRDX1 protein as a putative biomarker in estrogen receptor (ER)-positive breast cancer. Methods: An anti-PRDX1 antibody was validated in breast cancer cell lines using immunoblotting, immunohistochemistry and reverse phase protein array (RPPA) technology. PRDX1 protein expression was evaluated in two independent breast cancer cohorts, represented on a screening RPPA (n = 712) and a validation tissue microarray (n = 498). In vitro assays were performed exploring the functional contribution of PRDX1, with oxidative stress conditions mimicked via treatment with H2O2, peroxynitrite, or adenanthin, a PRDX1/2 inhibitor. Results: In ER-positive cases, high PRDX1 protein expression is a biomarker of improved prognosis across both cohorts. In the validation cohort, high PRDX1 expression was an independent predictor of improved relapse-free survival (hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.40 to 0.96, P = 0.032), breast cancer-specific survival (HR = 0.44, 95% CI = 0.24 to 0.79, P = 0.006) and overall survival (HR = 0.61, 95% CI = 0.44 to 0.85, P = 0.004). RPPA screening of cancer signaling proteins showed that ER alpha protein was upregulated in PRDX1 high tumors. Exogenous H2O2 treatment decreased ER alpha protein levels in ER-positive cells. PRDX1 knockdown further sensitized cells to H2O2- and peroxynitrite-mediated effects, whilst PRDX1 overexpression protected against this response. Inhibition of PRDX1/2 antioxidant activity with adenanthin dramatically reduced ER alpha levels in breast cancer cells. Conclusions: PRDX1 is shown to be an independent predictor of improved outcomes in ER-positive breast cancer. Through its antioxidant function, PRDX1 may prevent oxidative stress-mediated ER alpha loss, thereby potentially contributing to maintenance of an ER-positive phenotype in mammary tumors. These results for the first time imply a close connection between biological activity of PRDX1 and regulation of estrogen-mediated signaling in breast cancer.
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| 5. |
- Zepeda-Romero, L. C., et al.
(författare)
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Prediction of Retinopathy of Prematurity Using the Screening Algorithm WINROP in a Mexican Population of Preterm Infants
- 2012
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Ingår i: Archives of Ophthalmology. - 0003-9950. ; 130:6, s. 720-723
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To retrospectively validate the WINROP (weight, insulin-like growth factor I, neonatal, retinopathy of prematurity [ROP]) algorithm in identification of type 1 ROP in a Mexican population of preterm infants. Methods: In infants admitted to the neonatal intensive care unit at Hospital Civil de Guadalajara from 2005 to 2010, weight measurements had been recorded once weekly for 192 very preterm infants (gestational age [GA] <32 weeks) and for 160 moderately preterm infants (GA >= 32 weeks). Repeated eye examinations had been performed and maximal ROP stage had been recorded. Data are part of a case-control database for severe ROP risk factors. Results: Type 1 ROP was found in 51.0% of very preterm and 35.6% of moderately preterm infants. The WINROP algorithm correctly identified type 1 ROP in 84.7% of very preterm infants but in only 5.3% of moderately preterm infants. For infants with GA less than 32 weeks, the specificity was 26.6%, and for those with GA 32 weeks or more, it was 88.3%. Conclusions: In this Mexican population of preterm infants, WINROP detected type 1 ROP early in 84.7% of very preterm infants and correctly identified 26.6% of infants who did not develop type 1 ROP. Uncertainties in dating of pregnancies and differences in postnatal conditions may be factors explaining the different outcomes of WINROP in this population.
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