Production of single-domain magnetite throughout life by sockeye salmon, Oncorhynchus nerka

Although single-domain particles of biogenic magnetite have been found in different species of pelagic fishes, nothing is known about when it is synthesized, or about whether the time during life when it is produced is correlated with the development of responses to magnetic field stimuli. We have investigated production of biogenic magnetite suitable for use in magnetoreception in different life stages of the sockeye salmon, Oncorhynchus nerka (Walbaum). Sockeye salmon were chosen because responses in orientation arenas to magnetic field stimuli have been demonstrated in both fry and smolt stages of this species. We found significant quantities of single-domain magnetite in connective tissue from the ethmoid region of the skull of adult (4-year-old) sockeye salmon. The ontogenetic study revealed an orderly increase in the amount of magnetic material in the same region of the skull but not in other tissues of sockeye salmon fry, yearlings and smolts. The physical properties of this material closely matched those of magnetite particles extracted from the ethmoid tissue of the adult fish. We suggest that single-domain magnetite particles suitable for use in magnetoreception are produced throughout life in the ethmoid region of the skull in sockeye salmon. Based on theoretical calculations, we conclude that there are enough particles present in the skulls of the fry to mediate their responses to magnetic field direction. By the smolt stage, the amount of magnetite present in the front of the skull is sufficient to provide the fish with a magnetoreceptor capable of detecting small changes in the intensity of the geomagnetic field. Other tissues of the salmon, such as the eye and skin, often contained ferromagnetic material, although the magnetizations of these tissues were usually more variable than in the ethmoid tissue. These deposits of unidentified magnetic material, some of which may be magnetite, appear almost exclusively in adults and so would not be useful in magnetoreception by young fish. We suggest that tissue from within the ethmoid region of the skull in pelagic fishes is the only site yet identified where magnetite suitable for use in magnetoreception is concentrated

A Symplectic Integrator for Hill's Equations

Hill's equations are an approximation that is useful in a number of areas of astrophysics including planetary rings and planetesimal disks. We derive a symplectic method for integrating Hill's equations based on a generalized leapfrog. This method is implemented in the parallel N-body code, PKDGRAV and tested on some simple orbits. The method demonstrates a lack of secular changes in orbital elements, making it a very useful technique for integrating Hill's equations over many dynamical times. Furthermore, the method allows for efficient collision searching using linear extrapolation of particle positions.Comment: 15 pages, 2 figures; minor revisions; accepted for publication in the Astronomical Journa

Probing the shape and history of the Milky Way halo with orbital spectral analysis

Accurate phase-space coordinates (three components of position and velocity) of individual stars are rapidly becoming available with current and future resolved star surveys. These data will enable the computation of the full three-dimensional orbits of tens of thousands of stars in the Milky Way’s stellar halo. We demonstrate that the analysis of stellar halo orbits in frequency space can be used to construct a ‘frequency map’ which provides a highly compact, yet intuitively informative way to represent the six-dimensional halo phase-space distribution function. This representation readily reveals the most important major orbit families in the halo, and the relative abundances of the different orbit families, which in turn reflect the shape and orientation of the dark matter halo relative to the disc. We demonstrate the value of frequency space orbit analysis by applying the method to halo orbits in a series of controlled simulations of disc galaxies. We show that the disc influences the shape of the inner halo making it nearly oblate, but the outer halo remains largely unaffected. Since the shape of the halo varies with radius, the frequency map provides a more versatile way to identify major and minor orbit families than traditional orbit classification schemes. Although the shape of the halo varies with radius, frequency maps of local samples of halo orbits confined to the inner halo contain most of the information about the global shape of the halo and its major orbit families. Frequency maps show that adiabatic growth of a disc traps halo orbits in numerous resonant orbit families (i.e. having commensurable frequencies). The locations and strengths of these resonant families are determined by both the global shape of the halo and its stellar distribution function. If a good estimate of the Galactic potential in the inner halo (within ∼ 50 kpc) is available, the appearance of strong, stable resonances in frequency maps of halo orbits will allow us to determine the degree of resonant trapping induced by the disc potential. We show that if the Galactic potential is not known exactly, a measure of the diffusion rate of a large sample of ∼ 104 halo orbits can help distinguish between the true potential and an incorrect potential. The orbital spectral analysis methods described in this paper provide a strong complementarity to existing methods for constraining the potential of the Milky Way halo and its stellar distribution function

Synthesis of a prosthetic group for radiolabeling of Melanoma targeting peptide Re-CCMSH [abstract]

Abstract only availableThere is currently no cure for malignant melanoma and the best hope for a patient is early diagnosis and surgical excision. A promising approach to early cancer diagnosis is the use of radiolabeled peptides for tumor imaging. Dr. Quinn's lab has developed a cyclized peptide analog of alpha-Melanocyte stimulating hormone called ReCCMSH which binds to over expressed melanocortin-1 receptors on the tumor cells. A common radioimaging technique in nuclear medicine is positron emission tomography (PET). The radionuclide, fluorine-18, is widely used as a labeling agent for PET studies because of its 110 minute half life and low energy and is thus a good candidate for radiolabeling of our peptide. However, direct fluorination of the peptide is not possible. To radiolabel the peptide, a prosthetic group must be developed that can be attached to the peptide and act as a fluorine acceptor. This prosthetic group must not alter the biological properties of the peptide including receptor affinity, rapid body clearance, and absence of side reactions. The organic synthesis of this prosthetic group was the focus of my research. Previous attempts at radiolabeling of the conjugated peptide have been inefficient multi-step syntheses and thus impractical. For my research, a benzyl aldehyde was modified through a series of reactions to create carboxyl-3-cyano-4-N,N,N-trimethylanilinium triflate. This compound can be coupled to the end of the peptide and subsequently radiolabeled in one efficient step. The peptide was synthesized via solid phase peptide synthesis and cyclized via rhenium metal coordination. The actual radiolabeling of the conjugated peptide along with the in vivo biodistribution studies on mice will be pursued over the next academic year

Optimization of metal-cyclization of alpha-MSH peptide analogs used in the treatment and detection of melanoma

Abstract only availableOver the past few years Dr. Quinn and his lab have made significant progress in the development of a melanoma treatment drug. Based upon peptide analogs of the alpha-melanocyte stimulating hormone, Α-MSH, Dr. Quinn has developed a metal cyclized drug that shows very promising results in therapy as well as early detection/imaging of melanoma tumors. The cyclization of the peptide around a metal core was shown to greatly increase the affinity of the peptide for its target. There are slight problems with the cyclization process that needed to be resolved or limited in order to make the synthesis of the drug as efficient as possible. The primary problem with the cyclization of the peptide is the fact that two main products are produced. One of these products is caused by the histidine residue swinging down and binding with the metal core. Histidine is one of the four amino acids directly involved with receptor recognition and thus this product's tumor uptake is at least 50% lower. Three variables were explored in hopes of reducing this second unwanted product. A new and simpler process developed by Fridkin et. al. ¹ was first considered. HPLC was used to purify the two major products and their identities were confirmed using mass spectrometry. The new procedure proved to be slightly more effective as the old procedure. With the old procedure roughly 32.3% of the two major products were of the undesired compound, however, using this new procedure this was reduced to 23.4%. A variation of the new procedure was then tried. Instead of dissolving the linear peptide in water, as the procedure called to do, the peptide was dissolved using DMF. This modification showed a significant change in the percentage of the two products. Of the two major products only 12.8% of the total was of the unwanted product thus producing 87.2% of the desired cyclized peptide. Finally an addition of an extra amino acid residue near the beginning of the sequence was tried in hopes of moving the histidine residue far enough away from the metal core in order to limit their interaction. Current tests are still being performed to determine whether or not this will be successful. (1) Fridkin, G., Bonsera, T.A., Litman, P., and Gilon, C. Nucl. Med Biol 32, 39-50, 2005.Molecular Imaging Progra