Stacking interaction of nucleobases: NMR investigations

The stacking interaction between nucleic acid bases has been investigated by the determination of the self-association of 6-methylpurine in various mixtures of water and nonaqueous solvents in order to elucidate the solvent effect. The parameters of stacking association as well as of local solvent-solute interactions have been measured by means of NMR technique. The influences of local hydration and of solvent-solvent interactions on the stacking ability are discussed.Parts I and II see Schimmack 1975     

Increased prolactin in acute coronary syndromes as putative Co-activator of ADP-stimulated P-selectin expression.

Prolactin and leptin are newly recognized platelet co-stimulators due to enhancement of ADP-induced platelet aggregation. The aim of our study was to assess whether both hormones prolactin and leptin play a role as co-activators of platelet activation in patients with acute coronary syndromes. Twenty-one patients with acute coronary syndromes, 10 with stable angina pectoris and 10 controls were studied. Patients with acute coronary syndromes showed significantly higher prolactin and leptin values and a significant increased P-selectin expression on platelets compared to patients with stable angina pectoris or controls. However, patients with acute myocardial infarction as a subgroup of acute coronary syndromes showed the highest prolactin levels as well as ADP stimulated P-selectin expression. In the myocardial infarction subgroup prolactin values showed a significant correlation to ADP stimulated P-selectin expression on platelets (r (2)=0.41; p=0.025), whereas leptin was not correlated. Our data indicate an association between increased prolactin values and enhanced P-selectin expression on platelets in patients with acute coronary syndromes. Therefore, the stress hormone prolactin could be a co-stimulator of platelet activation in these patients. In contrast, the putative platelet activator leptin does not seem to play a major role in acute coronary syndromes.     

Adrenomedullin is a novel marker of tumor progression in neuroendocrine carcinomas.

Adrenomedullin is a multi-functional polypeptide hormone. Its involvement in angiogenesis and vasodilator action support the hypothesis that adrenomedullin may be a secretory product of neuroendocrine tumors and contribute to tumor progression. Plasma levels of adrenomedullin were measured by radioimmunoassay in 46 patients with neuroendocrine carcinomas of the gastroenteropancreatic and bronchial system. Tissue expression of adrenomedullin was studied using monoclonal antibodies on pretreated paraffin embedded tissues in a group of 31 patients. Adrenomedullin plasma levels were significantly elevated in patients compared to healthy age-matched controls (p < 0.001). The highest plasma levels were found in patients with neuroendocrine carcinomas of bronchial, midgut and unknown origin. Patients with progressive disease had higher plasma levels than patients with stable disease (p < 0.001). Of the examined tumor samples, 55 % showed cytoplasmic staining for adrenomedullin > 5 % of the total tumor area. Plasma levels and tissue expression of adrenomedullin did not correlate with functional activity of the tumors or presence of the carcinoid syndrome, but did with tumor progression (p < 0.001 and p < 0.014). In conclusion, plasma and tissue expression of the angiogenic peptide adrenomedullin are predictive of tumor progression in patients with neuroendocrine carcinomas. Adrenomedullin might represent a useful prognostic marker in patients with neuroendocrine carcinomas.     

Novel methods improve prediction of species' distributions from occurrence data

Prediction of species' distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence-only data to fit models, and independent presence-absence data to evaluate the predictions. Along with well-established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species' distributions. These include machine-learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species' occurrence data. Presence-only data were effective for modelling species' distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve.     

Influence of metal ions on systems of dimethylsulfoxide-uracil-derivatives: NMR investigations

Summary The NMR spectra of uracil and some of its derivatives have been investigated using deuterated dimethylsulfoxide as a solvent. The spectral positions of the peaks depend on the electron-attracting or -releasing strength of the substituents: rel. to uracil, the peaks were shifted upfleld in the case of the electron-releasing substituents andvice versa. A plot of the electron affinityvs. the H-3 position exhibits a straigth line. Addition of Cu²⁺ or other metal ions, such as Pe³⁺, Ni²⁺, Co²⁺, Zn²⁺, and Ag⁺, results in a splitting of the N-H protons, the distance of which turned out to be a linear relationship to the inverse electronegativity. K⁺, Na⁺, Mg²⁺, NH₄ ⁺, Cl^–, NO₃ ^–, SO₄ ^2– had no effect at all. The effect of Cu²⁺ and the substituents as well seems to be mediated by the hydrogen bond formed between the uracil derivative and DMSO.Dedicated to Professor Dr. Dr. h. c. mult. B. Rajewsky on the occasion of his 80th birthday.     

Compatibility of magnetic imprinting and secular variation

Diverse ocean migrants, including some sea turtles, elephant seals, and salmon, begin life in particular reproductive areas along coastlines, disperse across vast expanses of sea, and then return as adults to their natal areas to reproduce [1], [2] and [3]. Little is known about how such marine animals guide themselves to the correct coastal region from hundreds or thousands of kilometers away and after absences ranging in duration from a few months to a decade or more. One hypothesis is that animals imprint on the magnetic field of their home area and use this information to return [1]. The Earth's field varies predictably across the globe, so different geographic areas are marked by distinctive magnetic fields that might, in principle, provide unique magnetic signatures for natal areas [4]. A potentially serious complication for this hypothesis is that the Earth's field changes gradually over time [1] and [4], causing the magnetic signatures that define natal areas to slowly drift. This secular variation could make natal homing via magnetic imprinting impossible if the magnetic signatures moved too far from the natal area [1], [5] and [6]. To investigate whether magnetic imprinting is compatible with secular variation, we sought a species with a life history that poses challenges for the hypothesis, reasoning that if magnetic imprinting is consistent with natal homing under unfavorable circumstances, then it would also be plausible in most other cases. We chose the Kemp's ridley sea turtle (Lepidochelys kempii), an endangered species that ranges widely over the Gulf of Mexico, northern Caribbean, and the eastern U.S. coast, but returns to nest along a single, limited region of coastline in northern Mexico [7]. This species requires approximately 10–15 years to reach sexual maturity [7] and is thus absent from its natal area for much longer than animals such as salmon and elephant seals [2] and [3]. Given this long absence, the Kemp's ridley appears to be particularly susceptible to effects of secular variation if it relies on magnetic imprinting. The modeling results we report here show that the magnetic imprinting hypothesis can account for how the Kemp's ridley turtle returns to its natal region even after absences of a decade or more.     

Varying survival of motoneurons and activation of distinct molecular mechanism in response to altered peripheral myelin protein 22 gene dosage

Alteration in the expression level of peripheral myelin protein 22 (PMP22) is the most frequent cause for demyelinating neuropathies of Charcot-Marie-Tooth type. Here, we demonstrate a loss of motoneurons (MNs) in the spinal cords from transgenic mice over-expressing Pmp22 ( Pmp22 ^tg ) while mice lacking Pmp22 [ Pmp22 ^ko ; knockout (ko)] exhibited normal MN numbers at the symptomatic age of 60 days. In order to describe the molecular changes in affected MNs, these cells were isolated from lumbar spinal cords by laser-capture microdissection. Remarkably, the MNs of the Pmp22 ^ko and Pmp22 ^tg mice showed different expression profiles because of the altered Pmp22 expression. The changes in the expression profile of MNs from Pmp22 ^ko mice resemble those described in MNs from mice after nerve injury and included genes that had been described in neuronal growth and regeneration like Gap 43 and Sprr 11a. The changes detected in the expression pattern of MNs from Pmp22 ^tg mice exhibited fewer similarities to other expression patterns. The specific expression pattern in the MNs of the Pmp22 ^ko mice might contribute to the better survival of the MNs. Our study also revealed induction of genes like brain-expressed X-linked 1 ( Bex 1) and desmoplakin ( Dsp ) that had recently been found up-regulated in MNs of human amyotrophic lateral sclerosis patients.