Cyclotides Isolated from an Ipecac Root Extract Antagonize the Corticotropin Releasing Factor Type 1 Receptor

Cyclotides are plant derived, cystine-knot stabilized peptides characterized by their natural abundance, sequence variability and structural plasticity. They are abundantly expressed in Rubiaceae, Psychotrieae in particular. Previously the cyclotide kalata B7 was identified to modulate the human oxytocin and vasopressin G protein-coupled receptors (GPCRs), providing molecular validation of the plants’ uterotonic properties and further establishing cyclotides as valuable source for GPCR ligand design. In this study we screened a cyclotide extract derived from the root powder of the South American medicinal plant ipecac (Carapichea ipecacuanha) for its GPCR modulating activity of the corticotropin-releasing factor type 1 receptor (CRF1R). We identified and characterized seven novel cyclotides. One cyclotide, caripe 8, isolated from the most active fraction, was further analyzed and found to antagonize the CRF1R. A nanomolar concentration of this cyclotide (260 nM) reduced CRF potency by ∼4.5-fold. In contrast, caripe 8 did not inhibit forskolin-, or vasopressin-stimulated cAMP responses at the vasopressin V2 receptor, suggesting a CRF1R-specific mode-of-action. These results in conjunction with our previous findings establish cyclotides as modulators of both classes A and B GPCRs. Given the diversity of cyclotides, our data point to other cyclotide-GPCR interactions as potentially important sources of drug-like molecules

APPROXIMATE SOLUTION OF ELASTOPLASTIC PROBLEMS BASED ON THE MOREAU-YOSIDA THEOREM

We propose a new approach to the numerical solution of quasi-static elastic-plastic problems based on the Moreau-Yosida theorem. After the time discretization, the problem is expressed as an energy minimization problem for unknown displacement and plastic strain fields. The dependency of the minimization functional on the displacement is smooth whereas the dependency on the plastic strain is non-smooth. Besides, there exists an explicit formula, how to calculate the plastic strain from a given displacement field. This allows us to reformulate the original problem as a minimization problem in the displacement only. Using the Moreau-Yosida theorem from the convex analysis, the minimization functional in the displacements turns out to be Frechet-differentiable, although the hidden dependency on the plastic strain is non-differentiable. The seconds derivative exists everywhere apart from the elastic-plastic interface dividing elastic and plastic zones of the continuum. This motivates to implement a Newton-like method, which converges super-linearly as can be observed in our numerical experiments

Iowa Farm and Rural Life Poll: 2007 Summary Report

Iowa farm families have both hopes and concerns associated with changes unfolding across the state, especially those related to the rapid development of the “bioeconomy.” The increasing focus on renewable fuels, especially ethanol and biodiesel, brings both great expectations for grain prices and economic growth as well as worries about impacts on the environment and the structure of agriculture. The 2007 Iowa Farm and Rural Life Poll asked questions about these issues and related topics such as land use and future farm plans. The poll was created in 1982 by Iowa State University Extension, the Iowa Agriculture and Home Economics Experiment Station, and the Iowa Department of Agriculture and Land Stewardship. It partners Extension and research programs with the needs of farm families. Data collected on issues of importance to the farming community provide input to local, state, and national leaders in their decision making process. We thank the many farm families who responded to this year’s survey and appreciate their continued participation in the poll.https://lib.dr.iastate.edu/extension_communities_pubs/1015/thumbnail.jp

Thiol-gelatin-norbornene bioink for laser‐based high‐definition bioprinting

Two-photon polymerization (2PP) is a lithography-based 3D printing method allowing the fabrication of 3D structures with sub-micrometer resolution. This work focuses on the characterization of gelatin-norbornene (Gel-NB) bioinks which enables the embedding of cells via 2PP. The high reactivity of the thiol-ene system allows 2PP processing of cell-containing materials at remarkably high scanning speeds (1000 mm s(-1)) placing this technology in the domain of bioprinting. Atomic force microscopy results demonstrate that the indentation moduli of the produced hydrogel constructs can be adjusted in the 0.2-0.7 kPa range by controlling the 2PP processing parameters. Using this approach gradient 3D constructs are produced and the morphology of the embedded cells is observed in the course of 3 weeks. Furthermore, it is possible to tune the enzymatic degradation of the crosslinked bioink by varying the applied laser power. The 3D printed Gel-NB hydrogel constructs show exceptional biocompatibility, supported cell adhesion, and migration. Furthermore, cells maintain their proliferation capacity demonstrated by Ki-67 immunostaining. Moreover, the results demonstrate that direct embedding of cells provides uniform distribution and high cell loading independently of the pore size of the scaffold. The investigated photosensitive bioink enables high-definition bioprinting of well-defined constructs for long-term cell culture studies

Imaging morphological details and pathological differences of red blood cells using tapping-mode AFM

The surface topography of red blood cells (RBCs) was investigated under nearphysiological conditions using atomic force microscopy (AFM). An immobilization protocol was established where RBCs are coupled via molecular bonds of the membrane glycoproteins to wheat germ agglutinin (WGA), which is covalently and flexibly tethered to the support. This results in a tight but noninvasive attachment of the cells. Using tappingmode AFM, which is known as gentle imaging mode and therefore most appropriate for soft biological samples like erythrocytes, it was possible to resolve membrane skeleton structures without major distortions or deformations of the cell surface. Significant differences in the morphology of RBCs from healthy humans and patients with systemic lupus erythematosus (SLE) were observed on topographical images. The surface of RBCs from SLE patients showed characteristic circularshaped holes with approx. 200 nm in diameter under physiological conditions, a possible morphological correlate to previously published changes in the SLE erythrocyte membrane