Pressure dependence of side chain <Superscript>13</Superscript>C chemical shifts in model peptides Ac-Gly-Gly-Xxx-Ala-NH<Subscript>2</Subscript>

For evaluating the pressure responses of folded as well as intrinsically unfolded proteins detectable by NMR spectroscopy the availability of data from well-defined model systems is indispensable. In this work we report the pressure dependence of ¹³C chemical shifts of the side chain atoms in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH₂ (Xxx, one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of a number of nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The size of the polynomial pressure coefficients B ₁ and B ₂ is dependent on the type of atom and amino acid studied. For H^N, N and C^α the first order pressure coefficient B ₁ is also correlated to the chemical shift at atmospheric pressure. The first and second order pressure coefficients of a given type of carbon atom show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure also are weakly correlated. The downfield shifts of the methyl resonances suggest that gauche conformers of the side chains are not preferred with pressure. The valine and leucine methyl groups in the model peptides were assigned using stereospecifically ¹³C enriched amino acids with the pro-R carbons downfield shifted relative to the pro-S carbons.     

Little association of biological trait values with environmental variables in invasive alien round goby (Neogobius melanostomus)

The relative importance of species‐specific biological trait characteristics and environmental factors in invasions of nonindigenous species remains controversial because both have mostly been studied independently. Thus, the main objective of this study was to examine the correlation of biological traits with environmental variation in the globally invasive round goby Neogobius melanostomus from the upper Danube River. Based on a sample of 653 specimens along a continuous 200 km river pathway, links between nine environmental factors (substrate‐type, six water measurements, and the communities of fishes and macroinvertebrates) and seven biological traits (nutritional and energetic status, trade‐offs of parasite resistance and resource allocation, and three growth proxies) were analyzed. Biological trait values of N. melanostomus hardly correlated with the environment, could not explain invasion progress and imply a general low overall importance for invasion success. Instead, alternative individual life‐history trajectories appear to determine invasion success. This is in line with up to 15% of all specimens having outlying biological trait values of potential adaptive value, suggesting a considerable importance of adaptive trait variation among single individuals for the whole invasion progress. This “individual trait utility hypothesis” gives an alternative explanation for success of invasive species by single individuals carrying particular traits, and it should be specifically targeted and analyzed at currently invaded sites.     

Outgrowing olfactory axons contain the Reelin receptor VLDLR and navigate through the Reelin-rich cribriform mesenchyme

Chemosensory neurons in the olfactory epithelium (OE) project axonal processes to the olfactory bulb (OB) of the brain. During embryonic stages, on their trajectory to the OB, the outgrowing axons traverse the so-called cribriform mesenchyme, which is located between the OE and the OB. The molecular cues guiding these axons through the cribriform mesenchyme are largely unknown. To identify molecules influencing the axonal trajectory in the murine cribriform mesenchyme, we performed microarray analyses focusing on extracellular matrix (ECM) proteins present in this tissue. Thereby, the ECM protein Reelin turned out to be an interesting candidate. Reelin was found to be expressed by numerous cells in the cribriform mesenchyme during the embryonic stages when the first axons navigate from the OE to the OB. These cells were closely associated with olfactory axons and apparently lack glial and neuronal markers. In the mesenchyme underlying the OE, localization of the Reelin protein was not confined to the Reelin-expressing cells, but it was also observed to be widely distributed in the ECM—most prominently in regions traversed by olfactory axons. Importantly, these axons were found to be endowed with the Reelin receptor very-low-density lipoprotein receptor (VLDLR). Finally, Reelin expression was also detectable in neuronal cells of the OB, which are contacted by VLDLR-positive olfactory axons. In summary, the results of the present study suggest that a Reelin/VLDLR signaling pathway might contribute to the formation of olfactory projections to the OB and the establishment of initial contacts between the incoming axons and neurons in the OB. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Funding:  This work was supported by the Deutsche Forschungsgemeinschaft.     

Expression of cGMP signaling elements in the Grueneberg ganglion

The Grueneberg ganglion (GG) is a cluster of neurons localized to the vestibule of the anterior nasal cavity. Based on axonal projections to the olfactory bulb of the brain, as well as expression of olfactory receptors and the olfactory marker protein, it is considered a chemosensory subsystem. Recently, it was observed that in mice, GG neurons respond to cool ambient temperatures. In mammals, coolness-induced responses in highly specialized neuronal cells are supposed to rely on the ion channel TRPM8, whereas in thermosensory neurons of the nematode worm Caenorhabditis elegans, detection of environmental temperature is mainly mediated by cyclic guanosine monophosphate (cGMP) pathways, in which cGMP is generated by transmembrane guanylyl cyclases. To unravel the molecular mechanisms underlying coolness-induced responses in GG neurons, potential expression of TRPM8 in the murine GG was investigated; however, no evidence was found that this ion channel is present in the GG. By contrast, a substantial number of GG neurons was observed to express the transmembrane guanylyl cyclase subtype GC-G. In the nose, GC-G expression appears to be confined to the GG since it was not detectable in other nasal compartments. In the GG, coolness-stimulated responses are only observed in neurons characterized by the expression of the olfactory receptor V2r83. Interestingly, expression of GC-G in the GG was found in this V2r83-positive subpopulation but not in other GG neurons. In addition to GC-G, V2r83-positive GG cells also co-express the phosphodiesterase PDE2A. Thus, in summary, coolness-sensitive V2r83-expressing GG neurons are endowed with a cGMP cascade which might underlie thermosensitivity of these cells, similar to the cGMP pathway mediating thermosensation in neurons of C. elegans. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. J. Fleischer and K. Mamasuew contributed equally to this work.     

The anthropometric history of Argentina, Brazil and Peru during the 19th and early 20th century

This anthropometric study focuses on the histories of three important Latin American countries - Brazil, Peru, and Argentina - during the 19th century, and tests hypotheses concerning their welfare trends. While non-farm Brazil and Lima, Peru, started at relatively low height levels, Brazil made substantial progress in nutritional levels from the 1860s to the 1880s. In contrast, Lima remained at low levels. Argentinean men were tall to begin with, but heights stagnated until 1910. The only exception were farmers and landowners, who benefited from the export boom.     

Infections after bone allograft surgery: a prospective study by a hospital bone bank using frozen femoral heads from living donors

In the advent of the EU guidelines 2004/23/EG and 2006/17/EG requiring extensive safety and quality steps in bone banking, the prevalence and risk of infection disease transmission from bone allograft needs to be reconsidered. Therefore, we prospectively reviewed the screening process of bone donations and the outcome of surgeries utilizing bone allografts from our internal hospital bone bank with regard to infections according to CDC criteria. One-hundred and eighty-eight allogenic bone transplantation procedures in 160 patients were followed-up for 12–64 months (mean 32 months). Bacterial infection occurred in 11 patients, the overall infection rate therefore was 6.9%. After review of the clinical and intraoperative findings, none of the infections were likely to have been caused by the bone graft. Although no follow-up serologic testing was performed, no HIV of hepatitis infections were observed. Frozen bone allografts derived from live donors and provided by hospitals can generally be considered safe. However, without new and relevant clinical expertise, continuing this technique will be impeded by the new EU guidelines and their national implementations.     

Therapeutic implications of the enhanced short and long-term cytotoxicity of radiation treatment followed by oncolytic parvovirus H-1 infection in high-grade glioma cells

The prognosis of malignant brain tumors remains extremely bad in spite of moderate improvements of conventional treatments. A promising alternative approach is the use of oncolytic viruses. Strategies to improve viral toxicity include the combination of oncolytic viruses with standard therapies. Parvovirus H-1 (H-1PV) is an oncolytic virus with proven toxicity in glioma cells. Recently it has been demonstrated that the combination of ionizing radiation (IR) with H-1PV showed promising results. Previously irradiated glioma cells remained fully permissive for H-1PV induced cytotoxicity supporting the use of H-1PV for recurrent gliomas, which typically arise from irradiated cell clones. When glioma cells were infected with H-1PV shortly (24 h) after IR, cell killing improved and only the combination of both treatments lead to complete long-term tumor cell killing. The latter finding raises the question whether IR in combination with H-1PV exerts an additional therapeutic effect on highly resistant glioma stem cells. A likely translation into current clinical treatment protocols is to use stereotactic radiation of non-resectable recurrent gliomas followed by intratumoral injection of H-1PV to harvest the synergistic effects of combination treatment.