Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering

The molecular engineering of cell-instructive artificial extracellular matrices is a powerful means to control cell behavior and enable complex processes of tissue formation and regeneration. This work reports on a novel method to produce such smart biomaterials by recapitulating the crosslinking chemistry and the biomolecular characteristics of the biopolymer fibrin in a synthetic analog. We use activated coagulation transglutaminase factor XIIIa for site-specific coupling of cell adhesion ligands and engineered growth factor proteins to multiarm poly(ethylene glycol) macromers that simultaneously form proteolytically sensitive hydrogel networks in the same enzyme-catalyzed reaction. Growth factor proteins are quantitatively incorporated and released upon cell-derived proteolytic degradation of the gels. Primary stromal cells can invade and proteolytically remodel these networks both in an in vitro and in vivo setting. The synthetic ease and potential to engineer their physicochemical and bioactive characteristics makes these hybrid networks true alternatives for fibrin as provisional drug delivery platforms in tissue engineering.

Language Boxes: Bending the Host Language with Modular Language Changes

As domain-specific modeling begins to attract widespread acceptance, pressure is increasing for the development of new domain-specific languages. Unfortunately these DSLs typically conflict with the grammar of the host language, making it difficult to compose hybrid code except at the level of strings; few mechanisms (if any) exist to control the scope of usage of multiple DSLs; and, most seriously, existing host language tools are typically unaware of the DSL extensions, thus hampering the development process. Language boxes address these issues by offering a simple, modular mechanism to encapsulate (i) compositional changes to the host language, (ii) transformations to address various concerns such as compilation and highlighting, and (iii) scoping rules to control visibility of language extensions. We describe the design and implementation of language boxes, and show with the help of several examples how modular extensions can be introduced to a host language and environment.

A Gag peptide encompassing B- and T-cell epitopes of the caprine arthritis encephalitis virus functions as modular carrier peptide

Short synthetic peptides are important tools in biomedical research permitting to generate hapten specific polyclonal sera for analytical purposes or functional studies. In this paper we provide proof of principle that a peptide located in a highly conserved portion of the Gag protein of the caprine arthritis encephalitis virus and carrying an immunodominant T helper cell epitope functions as an efficient carrier peptide, mediating a strong antibody response to a peptidic hapten encompassing a well-characterized B cell epitope of Env. The carrier and hapten peptides were collinearly synthesized permutating their molecular arrangement. While the antibody response to the hapten was similar for both constructs, the antibody response to a B cell epitope overlapping the T helper cell epitope of the Gag carrier peptide was considerably different. This permits a modular use of the carrier peptide to generate antibody directed exclusively to the hapten peptide or a strong humoral response to both carrier- and hapten-peptide. Finally, we have mapped the epitopes involved in this polarized antibody response and discussed the potential immunological implications.

A modular LHC built on the DNA three-way junction

A light-harvesting complex composed of a p-stacked multichromophoric array in a DNA three-way junction is described. The modular design allows for a ready exchange of non-covalently attached energy acceptors

Plasticity to wind is modular and genetically variable in Arabidopsis thaliana

Thigmomorphogenesis, the characteristic phenotypic changes by which plants react to mechanical stress, is a widespread and probably adaptive type of phenotypic plasticity. However, little is known about its genetic basis and population variation. Here, we examine genetic variation for thigmomorphogenesis within and among natural populations of the model system Arabidopsis thaliana. Offspring from 17 field-collected European populations was subjected to three levels of mechanical stress exerted by wind. Overall, plants were remarkably tolerant to mechanical stress. Even high wind speed did not significantly alter the correlation structure among phenotypic traits. However, wind significantly affected plant growth and phenology, and there was genetic variation for some aspects of plasticity to wind among A. thaliana populations. Our most interesting finding was that phenotypic traits were organized into three distinct and to a large degree statistically independent covariance modules associated with plant size, phenology, and growth form, respectively. These phenotypic modules differed in their responsiveness to wind, in the degree of genetic variability for plasticity, and in the extent to which plasticity affected fitness. It is likely, therefore, that thigmomorphogenesis in this species evolves quasi-independently in different phenotypic modules.

A modular LHC built on the DNA three-way junction

Over the past years, in numerous studies the DNA double helix serves as a scaffold for the controlled arrangement of functional molecules, including a wide range of different chromophores. Other nucleic acid structures like the DNA three-way junction have been exploited for this purpose as well. Recently, the successful development of DNA-based light-harvesting antenna systems have been reported. Herein, we describe the use of the DNA three-way junction (3WJ) as a versatile scaffold for the modular construction of an artificial light harvesting complex (LHC). The LHC is based on a modular construction in which a phenanthrene antenna is located in one of the three stems and the acceptor is brought into proximity of the antenna through the annealing of the third strand. Phenanthrene excitation (320 nm) is followed by energy transfer to pyrene (resulting in exciplex emission), perylenediimide (quencher) or a cyanine dye (cyanine fluorescence).

Modular training in vascular and endovascular surgery exemplified by the Vascular International Foundation and School

The partial shift from patient to model is a reasonable and necessary paradigm shift in surgery in order to increase patient safety and to adapt to the reduced training time periods in hospitals and increased quality demands. Since 1991 the Vascular International Foundation and School has carried out many training courses with more than 2,500 participants. The modular build training system allows to teach many open vascular and endovascular surgical techniques on lifelike models with a pulsatile circulation. The simulation courses cannot replace training in operating rooms but are suitable for supporting the cognitive and associative stages for achieving motor skills. Scientific evaluation of the courses has continually shown that the training principle established since 1991 can lead to significant learning success. They are extremely useful not only for beginners but also for experienced vascular surgeons. They can help to shorten the learning curve, to learn new techniques or to refine previously used techniques in all stages of professional development. Keywords Advanced training · Advanced training regulations · Training model · Vascular International · Certification

Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization.

Virus-like particles (VLPs) are non-infectious self-assembling nanoparticles, useful in medicine and nanotechnology. Their repetitive molecularly-defined architecture is attractive for engineering multivalency, notably for vaccination. However, decorating VLPs with target-antigens by genetic fusion or chemical modification is time-consuming and often leads to capsid misassembly or antigen misfolding, hindering generation of protective immunity. Here we establish a platform for irreversibly decorating VLPs simply by mixing with protein antigen. SpyCatcher is a genetically-encoded protein designed to spontaneously form a covalent bond to its peptide-partner SpyTag. We expressed in E. coli VLPs from the bacteriophage AP205 genetically fused to SpyCatcher. We demonstrated quantitative covalent coupling to SpyCatcher-VLPs after mixing with SpyTag-linked to malaria antigens, including CIDR and Pfs25. In addition, we showed coupling to the VLPs for peptides relevant to cancer from epidermal growth factor receptor and telomerase. Injecting SpyCatcher-VLPs decorated with a malarial antigen efficiently induced antibody responses after only a single immunization. This simple, efficient and modular decoration of nanoparticles should accelerate vaccine development, as well as other applications of nanoparticle devices.