126 research outputs found
The effects of Cu and Fe availability on the growth and Cu : C ratios of marine diatoms
No full textWe investigated the effects of copper (Cu) and iron (Fe) availability on the growth rates, cellular Cu content, and steady-state Cu uptake rates of eight species of centric diatoms (coastal and oceanic strains). Whereas Fe and Cu availability had a significant effect on the growth rates of both costal and oceanic diatoms, an interaction between Fe and Cu availability and growth rates was only observed for the oceanic diatoms. Determination of cellular Cu : carbon (C) quotas using the radiotracers (67)Cu and (14)C revealed that under Cu-sufficient conditions oceanic diatoms had elevated Cu : C ratios relative to coastal strains, regardless of Fe availability. Two species (one oceanic and one coastal) significantly increased their Cu demands in response to Fe limitation, indicating upregulation of the Cu-dependent high-affinity Fe uptake system in these organisms. The changes in cellular Cu : C ratios were accompanied by variations in steady-state Cu uptake rates. Thus, in some cases Cu uptake rates appear to be regulated by the cell in response to Fe availability. Rates of Cu acquisition also responded significantly to Cu variability. The variation in Cu uptake was more closely correlated with changes in total Cu concentration in the medium than in inorganic, free Cu concentrations, implying that organic Cu complexes may be bioavailable to diatoms. These findings indicate a greater biological role for Cu than was previously thought in open ocean regions
Copper-uptake kinetics of coastal and oceanic diatoms
No full textWe investigated copper (Cu) acquisition mechanisms and uptake kinetics of the marine diatoms Thalassiosira oceanica Hasle, an oceanic strain, and Thalassiosira pseudonana Hasle et Heimdal, a coastal strain, grown under replete and limiting iron (Fe) and Cu availabilities. The Cu-uptake kinetics of these two diatoms followed classical Michaelis-Menten kinetics. Biphasic uptake kinetics as a function of Cu concentration were observed, suggesting the presence of both high- and low-affinity Cu-transport systems. The half-saturation constants (K(m)) and the maximum Cu-uptake rates (V(max)) of the high-affinity Cu-transport systems (similar to 7-350 nM and 1.5-17 zmol center dot mu m-2 center dot h-1, respectively) were significantly lower than those of the low-affinity systems (> 800 nM and 30-250 zmol center dot mu m-2 center dot h-1, respectively). The two Cu-transport systems were controlled differently by low Fe and/or Cu. The high-affinity Cu-transport system of both diatoms was down-regulated under Fe limitation. Under optimal-Fe and low-Cu growth conditions, the K(m) of the high-affinity transport system of T. oceanica was lower (7.3 nM) than that of T. pseudonana (373 nM), indicating that T. oceanica had a better ability to acquire Cu at subsaturating concentrations. When Fe was sufficient, the low-affinity Cu-transport system of T. oceanica saturated at 2,000 nM Cu, while that of T. pseudonana did not saturate, indicating different Cu-transport regulation by these two diatoms. Using CuEDTA as a model organic complex, our results also suggest that diatoms might be able to access Cu bound within organic Cu complexes
Herschel-ATLAS : deep HST/WFC3 imaging of strongly lensed submillimetre galaxies
No full textThis work is supported by STFC (grants PP/D002400/1 and ST/G002533/1)We report on deep near-infrared observations obtained with the Wide Field Camera-3 (WFC3) onboard the Hubble Space Telescope (HST) of the first five confirmed gravitational lensing events discovered by the Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS). We succeed in disentangling the background galaxy from the lens to gain separate photometry of the two components. The HST data allow us to significantly improve on previous constraints of the mass in stars of the lensed galaxy and to perform accurate lens modelling of these systems, as described in the accompanying paper by Dye et al. We fit the spectral energy distributions of the background sources from near-IR to millimetre wavelengths and use the magnification factors estimated by Dye et al. to derive the intrinsic properties of the lensed galaxies. We find these galaxies to have star-formations rates (SFR) ∼ 400–2000 M⊙ yr−1, with ∼(6–25) × 1010 M⊙ of their baryonic mass already turned into stars. At these rates of star formation, all remaining molecular gas will be exhausted in less than ∼100 Myr, reaching a final mass in stars of a few 1011 M⊙. These galaxies are thus proto-ellipticals caught during their major episode of star formation, and observed at the peak epoch (z ∼ 1.5–3) of the cosmic star formation history of the Universe.Peer reviewe
Titanium-45 (45Ti) Radiochemistry and Applications in Molecular Imaging
No full textMolecular imaging is an important part of modern medicine which enables the non-invasive identification and characterization of diseases. With the advancement of radiochemistry and scanner technology, nuclear medicine is providing insight into efficient treatment options for individual patients. Titanium-45 (45Ti) is a lesser-explored radionuclide that is garnering increasing interest for the development of positron emission tomography (PET) radiopharmaceuticals. This review discusses aspects of this radionuclide including production, purification, radiochemistry development, and molecular imaging studies
Peptide Based Imaging Agents for HER2 Imaging in Oncology
No full textBreast cancer continues to be the most lethal cancer type in women and one of the most diagnosed. Understanding Breast cancer receptor status is one of the most vital processes for determining treatment options. One type of breast cancer, human epidermal growth factor receptor 2 (HER2) positive, has approved receptor-based therapies including trastuzumab and pertuzumab that can significantly increase the likelihood of survival. Current methods to determine HER2 status include biopsies with immunohistochemical staining and/or fluorescence in situ hybridization. However, positron emission tomography (PET) imaging techniques using 89 Zr-trastuzumab or 89 Zr-pertuzumab are currently in clinical trials for a non-invasive, full body diagnostic approach. Although the antibodies have strong specificity to the HER2 positive lesions, challenges involving long post-injection time for imaging due to the blood circulation of the antibodies and matching of long-live isotopes leading to increased dose to the patient leave opportunities for alternative PET imaging probes. Peptides have been shown to allow for shorter injection-to-imaging time and can be used with shorter lived isotopes. HER2 specific peptides under development will help improve the diagnosis and potentially therapy options for HER2 positive breast cancer. Peptides showing specificity for HER2 could start widespread development of molecular imaging techniques for HER2 positive cancers
Positron Emission Tomography Imaging of Macrophages in Cancer
No full textMacrophages are large phagocytic cells that can be classified as a type of white blood cell and may be either mobile or stationary in tissues. The presence of macrophages in essentially every major disease makes them attractive candidates to serve as therapeutic targets and diagnostic biomarkers. Macrophages that are found in the microenvironment of solid tumors are referred to as tumor-associated macrophages (TAMs) and have been shown to influence chemoresistance, immune regulation, tumor initiation and tumor growth. The imaging of TAMs through Positron Emission Tomography (PET) has the potential to provide valuable information on cancer biology, tumor progression, and response to therapy. This review will highlight the versatility of macrophage imaging in cancer through the use of PET
The rise of metal radionuclides in medical imaging: copper-64, zirconium-89 and yttrium-86
No full text Positron emission tomography, with its high sensitivity and resolution, is growing rapidly as an imaging technology for the diagnosis of many disease states. The success of this modality is reliant on instrumentation and the development of effective and novel targeted probes. Initially, research in this area was focused on what we will define in this article as ‘standard’ PET isotopes (carbon-11, nitrogen-13, oxygen-15 and fluorine-18), but the short half-lives of these isotopes limit radiopharmaceutical development to those that probe rapid biological processes. To overcome these limitations, there has been a rise in nonstandard isotope probe development in recent years. This review focuses on the biological probes and processes that have been examined, in additiom to the preclinical and clinical findings with nonstandard radiometals: copper-64, zirconium-89, and yttrium-86. </jats:p
Evaluation of 68Ga-Radiolabeled Peptides for HER2 PET Imaging
No full textOne in eight women will be diagnosed with breast cancer in their lifetime and approximately 25% of those cases will be HER2-positive. Current methods for diagnosing HER2-positive breast cancer involve using IHC and FISH from suspected cancer biopsies to quantify HER2 expression. HER2 PET imaging could potentially increase accuracy and improve the diagnosis of lesions that are not available for biopsies. Using two previously discovered HER2-targeting peptides, we modified each peptide with the chelator DOTA and a PEG2 linker resulting in DOTA-PEG2-GSGKCCYSL (P5) and DOTA-PEG2-DTFPYLGWWNPNEYRY (P6). Each peptide was labeled with 68Ga and was evaluated for HER2 binding using in vitro cell studies and in vivo tumor xenograft models. Both [68Ga]P5 and [68Ga]P6 showed significant binding to HER2-positive BT474 cells versus HER2-negative MDA-MB-231 cells ([68Ga]P5; 0.68 ± 0.20 versus 0.47 ± 0.05 p < 0.05 and [68Ga]P6; 0.55 ± 0.21 versus 0.34 ± 0.12 p < 0.01). [68Ga]P5 showed a higher percent injected dose per gram (%ID/g) binding to HER2-positive tumors two hours post-injection compared to HER2-negative tumors (0.24 ± 0.04 versus 0.12 ± 0.06; p < 0.05), while the [68Ga]P6 peptide showed significant binding (0.98 ± 0.22 versus 0.51 ± 0.08; p < 0.05) one hour post-injection. These results lay the groundwork for the use of peptides to image HER2-positive breast cancer
- …
