Züchtungsmethoden in der Diskussion - Brauchen wir Kohl aus Protoplastenfusion?

Bei Kohl aus ökologischem Anbau scheiden sich die Bio-Geister: Kohrabi-, Brokkoli- und Blumenkohlsorten aus Europa und den USA werden zunehmend mit Hilfe umstrittener Züchtungsmethoden wie der gentechnik-nahen Protoplastenfusion angebaut. Werte des Ökolandbaus wie der Erhalt der Artenvielfalt und der Schutz der natürlichen Reproduktionsfähigkeit von Pflanzen werden durch solche Techniken in Frage gestellt. Warum und mit welchem Nutzen sich diese Züchtungsmethode in den letzten Jahren im Gemüseanbau etabliert hat, wird von Fachleuten unterschiedlich beantwortet. Nur mit welchen Konsequenzen? Was sind die Alternativen für Anbau und Handel? Die Protoplastenfusion wird bei Kohl angewendet, um die erbliche Pollensterilität (cytoplasmatic male sterility = CMS) des Rettichs auf verschiedene Kohlarten zu übertragen. Sie erleichtert die Züchtung von Hybriden, die mittlerweile auch im Öko-Landbau weit verbreitet sind - unverdientermaßen, aber das wäre ein weiteres Diskussionsthema..

Ribosome selectivity and nascent chain context in modulating the incorporation of fluorescent non-canonical amino acid into proteins

Fluorescence reporter groups are important tools to study the structure and dynamics of proteins. Genetic code reprogramming allows for cotranslational incorporation of non‑canonical amino acids at any desired position. However, cotranslational incorporation of bulky fluorescence reporter groups is technically challenging and usually inefficient. Here we analyze the bottlenecks for the cotranslational incorporation of NBD‑, BodipyFL‑ and Atto520‑labeled Cys‑tRNACys into a model protein using a reconstituted in‑vitro translation system. We show that the modified Cys‑tRNACys can be rejected during decoding due to the reduced ribosome selectivity for the modified aa‑tRNA and the competition with native near‑cognate aminoacyl‑tRNAs. Accommodation of the modified Cys‑tRNACys in the A site of the ribosome is also impaired, but can be rescued by one or several Gly residues at the positions −1 to −4 upstream of the incorporation site. The incorporation yield depends on the steric properties of the downstream residue and decreases with the distance from the protein N‑terminus to the incorporation site. In addition to the full‑length translation product, we find protein fragments corresponding to the truncated N‑terminal peptide and the C‑terminal fragment starting with a fluorescence‑labeled Cys arising from a StopGo‑like event due to a defect in peptide bond formation. The results are important for understanding the reasons for inefficient cotranslational protein labeling with bulky reporter groups and for designing new approaches to improve the yield of fluorescence‑ labeled protein

Oscillations in the expression of a self-repressed gene induced by a slow transcriptional dynamics

We revisit the dynamics of a gene repressed by its own protein in the case where the transcription rate does not adapt instantaneously to protein concentration but is a dynamical variable. We derive analytical criteria for the appearance of sustained oscillations and find that they require degradation mechanisms much less nonlinear than for infinitely fast regulation. Deterministic predictions are also compared with stochastic simulations of this minimal genetic oscillator

Oscillations in the expression of a self-repressed gene induced by a slow transcriptional dynamics

We revisit the dynamics of a gene repressed by its own protein in the case where the transcription rate does not adapt instantaneously to protein concentration but is a dynamical variable. We derive analytical criteria for the appearance of sustained oscillations and find that they require degradation mechanisms much less nonlinear than for infinitely fast regulation. Deterministic predictions are also compared with stochastic simulations of this minimal genetic oscillator

Atomic motion in tilted optical lattices

This paper presents a formalism describing the dynamics of a quantum particle in a one-dimensional, time-dependent, tilted lattice. The formalism uses the Wannier-Stark states, which are localized in each site of the lattice, and provides a simple framework allowing fully-analytical developments. Analytic solutions describing the particle motion are explicit derived, and the resulting dynamics is studied.Comment: 6 pages, 2 figs, submitted to EPJD, Springer Verlag styl

Surfactant protein-D and exposure to bioaerosols in wastewater and garbage workers

Purpose: Bioaerosols and their constituents, such as endotoxins, are capable of causing an inflammatory reaction at the level of the lung-blood barrier, which becomes more permeable. Thus, it was hypothesized that occupational exposure to bioaerosols can increase leakage of surfactant protein-D (SP-D), a lung-specific protein, into the bloodstream. Methods: SP-D was determined by ELISA in 316 wastewater workers, 67 garbage collectors, and 395 control subjects. Exposure was assessed with four interview-based indicators and by preliminary endotoxin measurements using the Limulus amoebocyte lysate assay. Influence of exposure on serum SP-D was assessed by multiple linear regression considering smoking, glomerular function, lung diseases, obesity, and other confounders. Results: Overall, mean exposure levels to endotoxins were below 100EU/m3. However, special tasks of wastewater workers caused higher endotoxin exposure. SP-D concentration was slightly increased in this occupational group and associated with the occurrence of splashes and contact to raw sewage. No effect was found in garbage collectors. Smoking increased serum SP-D. No clinically relevant correlation between spirometry results and SP-D concentrations appeared. Conclusions: These results support the hypothesis that inhalation of bioaerosols, even at low concentrations, has a subclinical effect on the lung-blood barrier, the permeability of which increases without associated spirometric change

Wavepacket reconstruction via local dynamics in a parabolic lattice

We study the dynamics of a wavepacket in a potential formed by the sum of a periodic lattice and of a parabolic potential. The dynamics of the wavepacket is essentially a superposition of ``local Bloch oscillations'', whose frequency is proportional to the local slope of the parabolic potential. We show that the amplitude and the phase of the Fourier transform of a signal characterizing this dynamics contains information about the amplitude and the phase of the wavepacket at a given lattice site. Hence, {\em complete} reconstruction of the the wavepacket in the real space can be performed from the study of the dynamics of the system.Comment: 4 pages, 3 figures, RevTex

Sample-Efficient Co-Design of Robotic Agents Using Multi-fidelity Training on Universal Policy Network

Co-design involves simultaneously optimizing the controller and agents physical design. Its inherent bi-level optimization formulation necessitates an outer loop design optimization driven by an inner loop control optimization. This can be challenging when the design space is large and each design evaluation involves data-intensive reinforcement learning process for control optimization. To improve the sample-efficiency we propose a multi-fidelity-based design exploration strategy based on Hyperband where we tie the controllers learnt across the design spaces through a universal policy learner for warm-starting the subsequent controller learning problems. Further, we recommend a particular way of traversing the Hyperband generated design matrix that ensures that the stochasticity of the Hyperband is reduced the most with the increasing warm starting effect of the universal policy learner as it is strengthened with each new design evaluation. Experiments performed on a wide range of agent design problems demonstrate the superiority of our method compared to the baselines. Additionally, analysis of the optimized designs shows interesting design alterations including design simplifications and non-intuitive alterations that have emerged in the biological world.Comment: 17 pages, 10 figure

2OACTIVATION OF T CELLS UPON TREATMENT WITH BISPECIFIC ANTIBODIES CORRELATES WITH THE EXPRESSION OF CO-INHIBITORY RECEPTORS ON TUMOR-INFILTRATING LYMPHOCYTES IN HUMAN LUNG CANCER

Introduction: T cell bispecific antibodies (TCB) are designed to recruit and simultaneously activate T cells against target cells such as tumor cells expressing a particular surface antigen. However, it is currently unknown how immuno-modulatory mechanisms active in the tumor microenvironment such as the expression of T cell co-inhibitory receptors may influence the therapeutic effect of TCBs. Methods: We performed a comprehensive phenotypic analysis of tumor infiltrating immune cells from lung carcinoma digests by multicolour flow cytometry. In particular, expression of T cell co-inhibitory and -stimulatory receptors was analyzed. Tumor digests were treated with catumaxomab, a TCB directed against CD3 and EpCAM. T cell activation and effector functions were assessed upon exposure to catumaxomab. Results: CD8+ T cells in lung carcinoma showed a broad heterogeneity in expression of the T cell co-inhibitory receptors PD-1, Tim-3, CTLA-4, Lag-3 and BTLA. Tumor stage and nodal status correlated with number and intensity of expressed receptors. Upon exposure to catumaxomab, a considerable heterogeneity in T cell activation among different tumors was observed. Of note, T cells expressing high levels and multiple co-inhibitory receptors were more impaired in their activation and effector functions after treatment with catumaxomab indicating a higher level of exhaustion. In a further analysis of CD8+ TIL subsets we found that BTLA+ T cells expressed more additional inhibitory receptors than all other subsets, namely PD-1, Tim-3, CTLA-4 and Lag-3, whereas only a small part of PD-1+ T cells expressed another receptor. Tim-3+ T cells usually co-expressed PD-1, but multiple receptors were found only on a low number of cells. Conclusion: In summary, our data suggest that the activity of TCBs is largely affected by the expression of T cell co-inhibitory receptors on tumor-infiltrating immune cells. Furthermore, these data provide a clinical rationale for combining bispecific antibodies with compounds which antagonize T cell exhaustion. Disclosure: D. Thommen, J. Schreiner, P. Herzig, P. Mueller and A. Zippelius: received research funding from Roche Glycart; V. Karanikas: is employed by Roche Glycart. All other authors have declared no conflicts of interes

Synonymous codons direct cotranslational folding toward different protein conformations.

In all genomes, most amino acids are encoded by more than one codon. Synonymous codons can modulate protein production and folding, but the mechanism connecting codon usage to protein homeostasis is not known. Here we show that synonymous codon variants in the gene encoding gamma-B crystallin, a mammalian eye-lens protein, modulate the rates of translation and cotranslational folding of protein domains monitored in real time by Forster resonance energy transfer and fluorescence-intensity changes. Gamma-B crystallins produced from mRNAs with changed codon bias have the same amino acid sequence but attain different conformations, as indicated by altered invivo stability and invitro protease resistance. 2D NMR spectroscopic data suggest that structural differences are associated with different cysteine oxidation states of the purified proteins, providing a link between translation, folding, and the structures of isolated proteins. Thus, synonymous codons provide a secondary code for protein folding in the cell