Comparative transcriptome analyses indicate molecular homology of zebrafish swimbladder and mammalian lung

10.1371/journal.pone.0024019PLoS ONE68

Investigation the influence of the presence of counter-enantiomers on the growth rate of enantiomers

Crystallisation can be an effective technology for the production of pure enantiomers. An interesting aspect in this context is the influence of the counter-enantiomer on the growth rate and morphology of a target enantiomer. Hereby the counter-enantiomer can be considered as an impurity with almost identical properties which is present in similar amounts as the target enantiomer. Two model systems have been studied: (a) conglomerate system threonine-H2O and (b) compound forming system mandelic acid-H2O. Two different observations were made. In system (a) no significant interdependence between the target and the counter-enantiomer on crystallization kinetics has been observed, i.e. the growth rates of the two enantiomers are independent. In contrast a strong influence of the presence of the counter-enantiomer on the growth rate could be observed in case of system (b). Moreover, it can be shown that the mandelic acid counter-enantiomer may even change the specific rates of growth for particular crystal faces which results in different crystal shapes (hexagonal for pure enantiomer in solution, rhombic for mixture of enantiomers). In theoretical investigations usually (effective) growth rates are considered to be proportional to the power of supersaturation of the crystallising compound: eq. 1 (attachment) Such an approach is not capable to describe the observations made for mandelic acid, where a modified growth rate law in which the dependence of the influence of both enantiomers on growth is needed: eq. 2 (attachment) In a theoretical study possible models are tested in order to describe the experimentally determined crystal growth rates for the mandelic acid enantiomers adequately. At first a one-dimensional population balance model (eq. 3) is applied capturing the interaction of both enantiomers: eq. 3 (attachment) where FN(k) denotes the particle size distribution with z being an effective length coordinate. To simulate a different evolution of the crystal faces a multidimensional treatment of this population problem has to be done. E. g. for the two-dimensional case with the two length coordinates y and z the following population balance equations must be solved in conjunction with the corresponding mass balances of the liquid phase: eq. 4 (attachment) To solve the problem stated numerically, newly developed high resolution adaptive discretisation methods are applied [4, 5] which will be also presented. [1] LORENZ, H.; PERLBERG, A.; SAPOUNDJIEV, D.; ELSNER, M.P.; SEIDEL-MORGENSTERN, A. (2006): Crystallization of enantiomers, 45(10), 863-873 [2] PERLBERG, A. (2006): Zur enantioselektiven Kristallisation aus Lösungen. Dissertation, Otto-von-Guericke-Universität Magdeburg [3] GRANDEURY, A.; LORENZ, H.; SEIDEL-MORGENSTERN, A. (2007): Impact of Heterochiral Interactions during the Growth of Enantiopure Materials: Example of Mandelic Acid (in preparation) [4] QAMAR, S.; ELSNER, M.P.; ANGELOV, I.; WARNECKE, G.; SEIDEL-MORGENSTERN, A. (2006): A Comparative Study of High Resolution Schemes for Solving Population Balances in Crystallization. Comp. Chem. Eng. 30(6-7), 1119-1131 [5] QAMAR, S.; ASHFAQ, A.; WARNECKE, G.; ANGELOV, I.; ELSNER, M.P.; SEIDEL-MORGENSTERN, A. (2006): Adaptive High Resolution Schemes for Multidimensional Population Balances in Crystallization Processes. Comp. & Chem. Eng. (in press), doi: 10.1016/j.compchemeng.2006.10.01

Adaptive high-resolution schemes for multidimensional population balances in crystallization processes

Crystallisation can be an effective technology for the production of pure enantiomers. An interesting aspect in this context is the influence of the counter-enantiomer on the growth rate and morphology of a target enantiomer. Hereby the counter-enantiomer can be considered as an impurity with almost identical properties which is present in similar amounts as the target enantiomer. Two model systems have been studied: (a) conglomerate system threonine-H₂O and (b) compound forming system mandelic acid-H₂O. Two different observations were made. In system (a) no significant interdependence between the target and the counter-enantiomer on crystallization kinetics has been observed, i.e. the growth rates of the two enantiomers are independent. In contrast a strong influence of the presence of the counter-enantiomer on the growth rate could be observed in case of system (b). Moreover, it can be shown that the mandelic acid counter-enantiomer may even change the specific rates of growth for particular crystal faces which results in different crystal shapes (hexagonal for pure enantiomer in solution, rhombic for mixture of enantiomers). In theoretical investigations usually (effective) growth rates are considered to be proportional to the power of supersaturation of the crystallising compound: eq. 1 (attachment) Such an approach is not capable to describe the observations made for mandelic acid, where a modified growth rate law in which the dependence of the influence of both enantiomers on growth is needed: eq. 2 (attachment) In a theoretical study possible models are tested in order to describe the experimentally determined crystal growth rates for the mandelic acid enantiomers adequately. At first a one-dimensional population balance model (eq. 3) is applied capturing the interaction of both enantiomers: eq. 3 (attachment) where F_N^(k) denotes the particle size distribution with z being an effective length coordinate. To simulate a different evolution of the crystal faces a multidimensional treatment of this population problem has to be done. E. g. for the two-dimensional case with the two length coordinates y and z the following population balance equations must be solved in conjunction with the corresponding mass balances of the liquid phase: eq. 4 (attachment) To solve the problem stated numerically, newly developed high resolution adaptive discretisation methods are applied [4, 5] which will be also presented. [1] LORENZ, H.; PERLBERG, A.; SAPOUNDJIEV, D.; ELSNER, M.P.; SEIDEL-MORGENSTERN, A. (2006): Crystallization of enantiomers, 45(10), 863-873 [2] PERLBERG, A. (2006): Zur enantioselektiven Kristallisation aus Lösungen. Dissertation, Otto-von-Guericke-Universität Magdeburg [3] GRANDEURY, A.; LORENZ, H.; SEIDEL-MORGENSTERN, A. (2007): Impact of Heterochiral Interactions during the Growth of Enantiopure Materials: Example of Mandelic Acid (in preparation) [4] QAMAR, S.; ELSNER, M.P.; ANGELOV, I.; WARNECKE, G.; SEIDEL-MORGENSTERN, A. (2006): A Comparative Study of High Resolution Schemes for Solving Population Balances in Crystallization. Comp. Chem. Eng. 30(6-7), 1119-1131 [5] QAMAR, S.; ASHFAQ, A.; WARNECKE, G.; ANGELOV, I.; ELSNER, M.P.; SEIDEL-MORGENSTERN, A. (2006): Adaptive High Resolution Schemes for Multidimensional Population Balances in Crystallization Processes. Comp. & Chem. Eng. (in press), doi: 10.1016/j.compchemeng.2006.10.01

Snord 3A: a molecular marker and modulator of prion disease progression.

Since preventive treatments for prion disease require early identification of subjects at risk, we searched for surrogate peripheral markers characterizing the asymptomatic phases of such conditions. To this effect, we subjected blood mRNA from E200K PrP CJD patients and corresponding family members to global arrays and found that the expression of Snord3A, a non-coding RNA transcript, was elevated several times in CJD patients as compared to controls, while asymptomatic carriers presented intermediate Snord3A levels. In the brains of TgMHu2ME199K mice, a mouse model mimicking for E200K CJD, Snord 3A levels were elevated in an age and disease severity dependent manner, as was the case for brains of these mice in which disease was exacerbated by copper administration. Snord3A expression was also elevated in scrapie infected mice, but not in PrP(0/0) mice, indicating that while the expression levels of this transcript may reflect diverse prion etiologies, they are not related to the loss of PrP(C)'s function. Elevation of Snord3A was consistent with the activation of ATF6, representing one of the arms of the unfolded protein response system. Indeed, SnoRNAs were associated with reduced resistance to oxidative stress, and with ER stress in general, factors playing a significant role in this and other neurodegenerative conditions. We hypothesize that in addition to its function as a disease marker, Snord3A may play an important role in the mechanism of prion disease manifestation and progression