- Using synovial volume measurement by MRI to evaluate the effect of 32P Radiation synovectomy on hemophilic arthropathy patients. [Journal Article]
- JXJ Xray Sci Technol 2019; 27(2):187-195
- CONCLUSIONS: The synovial membrane volume and MR enhancement ratio can be used to monitor patient response to PRS treatment.
- Phosphorylation of a serine/proline-rich motif in oxysterol binding protein-related protein 4L (ORP4L) regulates cholesterol and vimentin binding. [Journal Article]
- PlosPLoS One 2019; 14(3):e0214768
- The family of oxysterol binding protein (OSBP) and OSBP-related proteins (ORPs) mediate sterol and phospholipid transfer and signaling at membrane contact sites (MCS). The activity of OSBP at MCS is …
The family of oxysterol binding protein (OSBP) and OSBP-related proteins (ORPs) mediate sterol and phospholipid transfer and signaling at membrane contact sites (MCS). The activity of OSBP at MCS is regulated by phosphorylation, but whether this applies to ORPs is unknown. Here we report the functional characterization of a unique proline/serine-rich phosphorylation motif (S762SPSSPSS769) in the lipid binding OSBP-related domain of full-length ORP4L and a truncated variant ORP4S. Phosphorylation was confirmed by mass spectrometry and [32P]PO4 incorporation, and in silico and in vitro assays using purified ORP4L identified putative proline-directed kinases that phosphorylate the site. The functional significance of the phospho-site was assessed by mutating serine 762, S763, S766 and S768 to aspartate or alanine to produce phosphomimetic (S4D) and phosphorylation-deficient (S4A) mutants, respectively. Solution binding of 25-hydroxycholesterol and cholesterol by recombinant ORP4L-S4D and -S4A was similar to wild-type but ORP4L-S4D more effectively extracted cholesterol from liposomes. ORP4L homo-dimerization was unaffected by phosphorylation but gel filtration of ORP4L-S4D indicated that the native conformation was affected. Confocal microscopy revealed that ORP4L-S4D also strongly associated with bundled vimentin filaments, a feature shared with ORP4S which lacks the PH and dimerization domains. We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.
- Monte Carlo dosimetry for a new 32P brachytherapy source using FLUKA code. [Journal Article]
- JCJ Contemp Brachytherapy 2019; 11(1):76-90
- CONCLUSIONS: This work fully characterizes dosimetric parameters of the sheathed and unsheathed new 32P brachytherapy sources in water and different tissue phantoms by using FLUKA code. The results demonstrate that the dose distribution in water differed from the calculated ones in tissue phantoms due to the densities and atomic composition for tissues that are not taken account by the TG-60 formalism.
- A cell-based high-throughput screen identifies tyrphostin AG 879 as an inhibitor of animal cell phospholipid and fatty acid biosynthesis. [Journal Article]
- BBBiochem Biophys Rep 2019; 18:100621
- Inhibition of animal cell phospholipid biosynthesis has been proposed for anticancer and antiviral therapies. Using CHO-K1 derived cell lines, we have developed and used a cell-based high-throughput …
Inhibition of animal cell phospholipid biosynthesis has been proposed for anticancer and antiviral therapies. Using CHO-K1 derived cell lines, we have developed and used a cell-based high-throughput procedure to screen a 1280 compound, small molecule library for inhibitors of phospholipid biosynthesis. We identified tyrphostin AG 879 (AG879), which inhibited phospholipid biosynthesis by 85-90% at a concentration of 10 μM, displaying an IC50 of 1-3 μM. The synthesis of all phospholipid head group classes was heavily affected. Fatty acid biosynthesis was also dramatically inhibited (90%). AG879 inhibited phospholipid biosynthesis in all additional cell lines tested, including MDCK, HUH7, Vero, and HeLa cell lines. In CHO cells, AG879 was cytostatic; cells survived for at least four days during exposure and were able to divide following its removal. AG879 is an inhibitor of receptor tyrosine kinases (RTK) and inhibitors of signaling pathways known to be activated by RTK's also inhibited phospholipid biosynthesis. We speculate that inhibition of RTK by AG879 results in an inhibition of fatty acid biosynthesis with a resulting decrease in phospholipid biosynthesis and that AG879's effect on fatty acid synthesis and/or phospholipid biosynthesis may contribute to its known capacity as an effective antiviral/anticancer agent.
- Quantum Dynamics Calculations of Na (32S, 32P) + HF → NaF + H Reactions. [Journal Article]
- JPJ Phys Chem A 2019 Apr 04; 123(13):2601-2609
- The dynamics of the reactive scatterings of the ground (Na(3S)) and first excited (Na(3P)) state sodium atoms from hydrogen fluoride (HF) molecules is investigated by performing comprehensive Corioli…
The dynamics of the reactive scatterings of the ground (Na(3S)) and first excited (Na(3P)) state sodium atoms from hydrogen fluoride (HF) molecules is investigated by performing comprehensive Coriolis-coupled quantum wave packet calculations on the recent ab initio potential energy surface (PES). In the Na(3S) + HF reaction, the nonadiabatic effect is found to be negligibly small, and the reactivity is significantly promoted by the initial vibrational excitations being in line with the available experimental result. Excellent quantitative agreement between theory and experiment is also achieved for the initial state specified integral cross sections and rate constants for v ≥ 3 vibrational states. However, the calculated rate constant for v = 2 significantly underestimates the experimental result. The possible cause for the disagreement is discussed in detail. For the Na(3P) + HF scattering, which can lead to the formation of either the ground state NaF + H product or Na(3S) + HF reactant via the harpooning process, the calculated result for the integral cross section shows excellent agreement with the available experimental result indicating the reasonable accuracy of the interstate coupling term of the employed PES.
- Quantification of dose-mortality responses in adult Diptera: Validation using Ceratitis capitata and Drosophila suzukii responses to spinosad. [Journal Article]
- PlosPLoS One 2019; 14(2):e0210545
- Quantitative laboratory bioassay methods are required to evaluate the toxicity of novel insecticidal compounds for pest control and to determine the presence of resistance traits. We used a radioacti…
Quantitative laboratory bioassay methods are required to evaluate the toxicity of novel insecticidal compounds for pest control and to determine the presence of resistance traits. We used a radioactive tracer based on 32P-ATP to estimate the volume of a droplet ingested by two dipteran pests: Ceratitis capitata (Tephritidae) and Drosophila suzukii (Drosophilidae). Using blue food dye it was possible to distinguish between individuals that ingested the solution from those that did not. The average volume ingested by C. capitata adults was 1.968 μl. Females ingested a ~20% greater volume of solution than males. Adults of D. suzukii ingested an average of 0.879 μl and females ingested ~30% greater volume than males. The droplet feeding method was validated using the naturally-derived insecticide spinosad as the active ingredient (a.i.). For C. capitata, the concentration-mortality response did not differ between the sexes or among three different batches of insects. Lethal dose values were calculated based on mean ingested volumes. For C. capitata LD50 values were 1.462 and 1.502 ng a.i./insect for males and females, respectively, equivalent to 0.274 and 0.271 ng a.i./mg for males and females, respectively, when sex-specific variation in body weight was considered. Using the same process for D. suzukii, the LD50 value was estimated at 2.927 ng a.i./insect, or 1.994 ng a.i./mg based on a mean body weight of 1.67 mg for both sexes together. We conclude that this technique could be readily employed for determination of the resistance status and dose-mortality responses of insecticidal compounds in many species of pestiferous Diptera.
- Study of fast and slow consecutive processes by heterogeneous isotope exchange using P-32 radiotracer. [Journal Article]
- JRJ Radioanal Nucl Chem 2018; 318(3):2349-2353
- The sorption of phosphate on soils is studied by radioisotopic tracer method. Two consecutive processes with rather different rates were differentiated: namely the heterogeneous isotope exchange betw…
The sorption of phosphate on soils is studied by radioisotopic tracer method. Two consecutive processes with rather different rates were differentiated: namely the heterogeneous isotope exchange between the phosphate in the soil solution and the weakly sorbed phosphate (fast reaction), and the transformation of weakly sorbed phosphate to tightly sorbed phosphate (slow reaction). In this paper, it is shown how the rate constants of these two processes can be determined by a radiotracer with a relatively short half-life.
- Image-guided brachytherapy in cervical cancer: Experience in the Complejo Hospitalario de Navarra. [Journal Article]
- RPRep Pract Oncol Radiother 2018 Nov-Dec; 23(6):510-516
- CONCLUSIONS: Use of interstitial HDR-BQ guided by RM increased CTV-HR dose and local control, like EMBRACE results. Nodal boost improves RDFS and perhaps OS.
- Calculation of productions of medical 201Pb, 198Au, 186Re, 111Ag, 103Pd, 90Y, 89Sr, 77Kr, 77As, 67Cu, 64Cu, 47Sc and 32P nuclei used in cancer therapy via phenomenological and microscopic level density models. [Journal Article]
- ARAppl Radiat Isot 2019; 144:64-79
- In the present study, we have widely investigated the production of nuclei used in cancer therapy for both phenomenological and microscopic level density models via TALYS and EMPIRE codes. To estimat…
In the present study, we have widely investigated the production of nuclei used in cancer therapy for both phenomenological and microscopic level density models via TALYS and EMPIRE codes. To estimate the production of the radioisotope, we calculated the cross-section curves of the reaction and the integral yield curves for nine level density models using the cross-sections and the mass-stopping powers acquired from X-PMSP program in the particle beam current of 1 μA and irradiation time 1 h. To discuss the obtained results on the basis of the cross-sections and the integral yields curves, the results were compared with the experimental data and the recommended data in the literature.
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- Photoinactivation of the Staphylococcus aureus Lactose-Specific EIICB Phosphotransferase Component with p-azidophenyl-β-D-Galactoside and Phosphorylation of the Covalently Bound Substrate. [Journal Article]
- JMJ Mol Microbiol Biotechnol 2018; 28(3):147-158
- CONCLUSIONS: Phosphorylation of the -OH group at C6 of p-nitrenephenyl-β-D-galactopyranoside covalently bound to EIICLac by the histidyl-phosphorylated [32P]P∼EIIBLac domain is a likely explanation for the observed acid resistance. Placing p-nitrenephenyl-β-D-galactopyranoside into the active site of modelled EIICLac suggested that the nitrene binds to the -NH- group of Ser248, which would explain why no sequence data beyond Pro247could be obtained.