The FeoB family of membrane embedded G proteins are involved with high affinity Fe(II) uptake in prokaryotes. Here, we report that FeoB harbors a novel GDP dissociation inhibitor-like domain that specifically stabilizes GDP-binding through an interaction with the switch I region of the G protein. We show that the stabilization of GDP binding is conserved between species despite a high degree of sequence variability in their guanine nucleotide dissociation inhibitor (GDI)-like domains, and demonstrate that the presence of the membrane embedded domain increases GDP-binding affinity roughly 150-fold over the level accomplished by action of the GDI-like domain alone. To our knowledge, this is the first example for a prokaryotic GDI, targeting a bacterial G protein-coupled membrane process. Our findings suggest that Fe(II) uptake in bacteria involves a G protein regulatory pathway reminiscent of signaling mechanisms found in higher-order organisms.

We investigate inclusive prompt photon and semi-inclusive prompt photon-hadron production in high energy proton-nucleus collisions using the Color Glass Condensate (CGC) formalism which incorporates non-linear dynamics of gluon saturation at small x via Balitsky-Kovchegov equation with running coupling. For inclusive prompt photon production, we rewrite the cross-section in terms of direct and fragmentation contributions and show that the direct photon (and isolated prompt photon) production is more sensitive to gluon saturation effects. We then analyze azimuthal correlations in photon-hadron production in high energy proton-nucleus collisions and obtain a strong suppression of the away-side peak in photon-hadron correlations at forward rapidities, similar to the observed mono-jet production in deuteron-gold collisions at forward rapidity at RHIC. We make predictions for the nuclear modification factor R p(d)A and photon-hadron azimuthal correlations in proton(deuteron)-nucleus collisions at RHIC and the LHC at various rapidities.

No abstract

No abstract

BackgroundIn recent years, Copper-64 (T1/2 = 12.7 h) in the chemical form of copper dichloride ([64Cu]CuCl2) has been identified as a potential agent for PET imaging and radionuclide therapy targeting the human copper transporter 1, which is overexpressed in a variety of cancer cells. Limited human biodistribution and radiation dosimetry data is available for this tracer. The aim of this research was to determine the biodistribution and estimate the radiation dosimetry of [64Cu]CuCl2, using whole-body (WB) PET scans in healthy volunteers. Six healthy volunteers were included in this study (3 women and 3 men, mean age ± SD, 54.3 ± 8.6 years; mean weight ± SD, 77.2 ± 12.4 kg). After intravenous injection of the tracer (4.0 MBq/kg), three consecutive WB emission scans were acquired at 5, 30, and 60 min after injection. Additional scans were acquired at 5, 9, and 24 h post-injection. Low-dose CT scan without contrast was used for anatomic localization and attenuation correction. OLINDA/EXM software was used to calculate human radiation doses using the reference adult model.ResultsThe highest uptake was in the liver, followed by lower and upper large intestine walls, and pancreas, in descending order. Urinary excretion was negligible. The critical organ was liver with a mean absorbed dose of 310 ± 67 μGy/MBq for men and 421 ± 56 μGy/MBq for women, while the mean WB effective doses were 51.2 ± 3.0 and 61.8 ± 5.2 μSv/MBq for men and women, respectively.ConclusionsTo the best of our knowledge, this is the first report on biodistribution and radiation dosimetry of [64Cu]CuCl2 in healthy volunteers. Measured absorbed doses and effective doses are higher than previously reported doses estimated with biodistribution data from patients with prostate cancer, a difference that could be explained not just due to altered biodistribution in cancer patients compared to healthy volunteers but most likely due to the differences in the analysis technique and assumptions in the dose calculation.

Thulium‐170 [T1/2 = 128.4 days, Eβ(max) = 968 keV, Eγ = 84 keV (3.26%)] has radionuclidic properties suitable for use in therapy. 170Tm can be produced by a relatively feasible route involving thermal neutron bombardment on natural Tm(NO3)3 (100% 169Tm) in medium flux research reactors. The combination of beta‐particle emission of Tm‐170 with therapeutic properties of C225 monoclonal antibody (cetuximab) as well as optimization studies for future Tm‐167 labeling was targeted in this study. Conjugated cetuximab was obtained by the addition of 0.5 ml of a cetuximab pharmaceutical solution (1 mg, in phosphate buffer, pH 7.8) to a glass tube pre‐coated with in situ prepared 1,4,7,10‐tetraazacyclododecane‐N,N,N,N‐tetraacetic acid mono‐(N‐hydroxysuccinimidyl) ester (DOTA‐NHS) (~5 mg) at 25°C. Cetuximab was labeled with 170Tm‐Thulium chloride (100 MBq) after conjugation with DOTA‐NHS in 2–3 h (radiochemical purity >99%, instant thin‐layer chromatography, specific activity = 77–385 TBq/mmol). Biodistribution studies in wild‐type rats for free Tm‐170 and the radioimmunoconjugate were performed to determine the distribution up to 72 h. A comparative time‐frame study was performed for critical organs for both radiochemical species. The major organs of accumulation were shown to be the lung, liver, and spleen, respectively. Copyright © 2012 John Wiley & Sons, Ltd.

The increasing clinical importance of drug‐resistant fungal pathogens has lent additional urgency to microbiological and antifungal research. Various thiazolo(or 1,2,3‐thiadiazolo)thiosemicarbazides (2a—2e), 3‐thiono‐1,4‐dihydrotriazolothiazoles‐(or 1,2,3‐thiadiazoles) (3a—3e), their related substituted thio‐4H‐1,2,4‐triazoles (4a—4p) and sulfones (5a—5o) were synthesized. Most of the compounds tested for antifungal activity exhibited significant effects against Cryptococcus neoofrmans and Sacchromyces cerevisiae at MIC ranges of 0.53 to 12.5μg/mL, whereas their activities were moderate against Candida albicans and weak against Aspergillus fumigatus. At 10 ppm concentration, all compounds showed low toxicity on brine shrimps (higher than 80% survival), except compounds 4c and 2c. At 100 ppm concentration most of the compounds showed toxicity except compounds 2b, 2e, 3c, 3d, 3e, and 4e. Compounds 4b, 4c, and 4h showed in vitro cytotoxicity against Kbalb cell lines and compounds 4c and 4g against 143B cell lines at 0.1 mM concentration.

Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging due to their unique magnetic and optical characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) are the prosperous group of NPs with the capability to apply as magnetic resonance imaging (MRI) contrast agents. Radiolabeling of targeted SPIONs with positron emitters can develop dual positron emission tomography (PET)/MRI agents to achieve better diagnosis of clinical conditions. Methods: In this work, N,N,N-trimethyl chitosan (TMC)-coated magnetic nanoparticles (MNPs) conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) as a radioisotope chelator and bombesin (BN) as a targeting peptide (DOTA-BN-TMC-MNPs) were prepared and validated using fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and powder X-ray diffraction (PXRD) tests. Final NPs were radiolabeled with gallium-68 (68 Ga) and evaluated in vitro and in vivo as a potential PET/MRI probe for breast cancer (BC) detection. Results: The DOTA-BN-TMC-MNPs with a particle size between 20 and 30 nm were efficiently labeled with 68 Ga (radiochemical purity higher than 98% using thin layer chromatography (TLC)). The radiolabeled NPs showed insignificant toxicity (.74% cell viability) and high affinity (IC 50 =8.79 µg/mL) for the gastrin-releasing peptide (GRP)-avid BC T-47D cells using competitive binding assay against 99m Tc-hydrazinonicotinamide (HYNIC)-gamma-aminobutyric acid (GABA)-BN (7-14). PET and MRI showed visible uptake of NPs by T-47D tumors in xenograft mouse models. Conclusion: 68 Ga-DOTA-BN-TMC-MNPs could be a potential diagnostic probe to detect BC using PET/MRI technique.