D,L-Cyclic Peptides as Structural Materials

The bioengineer has a choice of building with proteins, peptides, polymers, nucleic acids, lipids, metals and minerals, each class containing tremendous diversity within its category. While the platforms are diverse, they can be unified by a common goal: to engineer nano- and micro-scale order to improve functionality. In doing so, self-assembling systems aim to bring the lessons learned from the order in natural systems83 into the therapeutics, materials, and electronics that society uses every day. The rigid geometry and tunable chemistry of D,L-cyclic peptides make them an intriguing building-block for the rational design of nano- and microscale hierarchically structured materials. Herein, we utilize a combination of electron microscopy, nanomechanical characterization including depth sensing-based bending experiments, and molecular modeling methods to obtain the structural and mechanical characteristics of cyclo-[(Gln-D-Leu)4] (QL4) assemblies. QL4 monomers assemble to form large, rod-like structures with diameters up to 2 μm and lengths of 10s to 100s of μm. Image analysis suggests that large assemblies are hierarchically organized from individual tubes that undergo bundling to form larger structures. With an elastic modulus of 11.3 ± 3.3 GPa, hardness of 387 ± 136 MPa and strength (bending) of 98 ± 19 MPa the peptide crystals are among the most robust known proteinaceous micro- and nano-fibers. The measured bending modulus of micron-scale fibers (10.5 ± 0.9 GPa) is in the same range as the Young’s modulus measured by nanoindentation indicating that the robust nanoscale network from which the assembly derives its properties is preserved at larger length-scales. Materials selection charts are used to demonstrate the particularly robust properties of QL4 including its specific flexural modulus in which it outperforms a number of biological proteinaceous and non-proteinaceous materials including collagen and enamel. We then demonstrate a composite approach to mechanical reinforcement of polymeric systems by incorporating synthetic D,L-cyclic peptide nanotube bundles as a structural filler in electrospun poly D-, L-lactic acid fibers. With 8 wt% peptide loading, the composite fibers are >5-fold stiffer than fibers composed of the polymer alone, according to AFM-based indentation experiments. The facile synthesis, high modulus, and low density, and reinforcing capabilities of QL4 fibers indicate that they may find utility as a filler material in a variety of high efficiency, biocompatible composite materials. This study represents the first experimental mechanical characterization of D,L-cyclic peptide assemblies or composites.Engineering and Applied Sciences - Engineering Science

Intelligent Queries over BIRN Data using the Foundational Model of Anatomy and a Distributed Query-Based Data Integration System

We demonstrate the usefulness of the Foundational Model of Anatomy (FMA) ontology in reconciling different neuroanatomical parcellation schemes in order to facilitate automatic annotation and “intelligent” querying and visualization over a large multisite fMRI study of schizophrenic versus normal controls

Enabling RadLex with the Foundational Model of Anatomy Ontology to Organize and Integrate Neuro-imaging Data

In this study we focused on empowering RadLex with an ontological framework and additional content derived from the Foundational Model of Anatomy Ontology1 thereby providing RadLex the facility to correlate the different standards used in annotating neuroradiological image data. The objective of this work is to promote data sharing, data harmonization and interoperability between disparate neuroradiological labeling systems

Mechanical Reinforcement of Polymeric Fibers through Peptide Nanotube Incorporation

High aspect ratio nanotubular assemblies can be effective fillers in mechanically reinforced composite materials. However, most existing nanotubes used for structural purposes are limited in their range of mechanical, chemical, and biological properties. We demonstrate an alternative approach to mechanical reinforcement of polymeric systems by incorporating synthetic d,l-cyclic peptide nanotube bundles as a structural filler in electrospun poly d-, l-lactic acid fibers. The nanotube bundles self-assemble through dynamic hydrogen bonding from synthetic cyclic peptides to yield structures whose dimensions can be altered based on processing conditions, and can be up to hundreds of micrometers long and several hundred nanometers wide. With 8 wt % peptide loading, the composite fibers are >5-fold stiffer than fibers composed of the polymer alone, according to atomic force microscopy-based indentation experiments. This represents a new use for self-assembling cyclic peptides as a load-bearing component in biodegradable composite materials.Engineering and Applied Science

Hydrothermal discharge during submarine eruptions : the importance of detection, response, and new technology

Author Posting. © The Oceanography Society, 2012. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 25, no. 1 (2012): 128–141, doi:10.5670/oceanog.2012.11.Submarine volcanic eruptions and intrusions construct new oceanic crust and build long chains of volcanic islands and vast submarine plateaus. Magmatic events are a primary agent for the transfer of heat, chemicals, and even microbes from the crust to the ocean, but the processes that control these transfers are poorly understood. The 1980s discovery that mid-ocean ridge eruptions are often associated with brief releases of immense volumes of hot fluids ("event plumes") spurred interest in methods for detecting the onset of eruptions or intrusions and for rapidly organizing seagoing response efforts. Since then, some 35 magmatic events have been recognized and responded to on mid-ocean ridges and at seamounts in both volcanic arc and intraplate settings. Field responses at mid-ocean ridges have found that event plumes occur over a wide range of eruption styles and sizes, and thus may be a common consequence of ridge eruptions. The source(s) of event plume fluids are still debated. Eruptions detected at ridges generally have high effusion rates and short durations (hours to days), whereas field responses at arc volcanic cones have found eruptions with very low effusion rates and durations on the scale of years. New approaches to the study of submarine magmatic events include the development of autonomous vehicles for detection and response, and the establishment of permanent seafloor observatories at likely future eruption sites.Support for these efforts came from the NOAA Vents Program and the National Science Foundation, primarily through its long-term funding of the RIDGE and Ridge 2000 Programs, including grants OCE-9812294 and OCE-0222069. SOSUS detection efforts were supported from 2006 to 2009 by the National Science Foundation, grant OCE-0623649

Natural genetic variation in <i>Arabidopsis thaliana</i> defense metabolism genes modulates field fitness

Natural populations persist in complex environments, where biotic stressors, such as pathogen and insect communities, fluctuate temporally and spatially. These shifting biotic pressures generate heterogeneous selective forces that can maintain standing natural variation within a species. To directly test if genes containing causal variation for the Arabidopsis thaliana defensive compounds, glucosinolates (GSL) control field fitness and are therefore subject to natural selection, we conducted a multi-year field trial using lines that vary in only specific causal genes. Interestingly, we found that variation in these naturally polymorphic GSL genes affected fitness in each of our environments but the pattern fluctuated such that highly fit genotypes in one trial displayed lower fitness in another and that no GSL genotype or genotypes consistently out-performed the others. This was true both across locations and within the same location across years. These results indicate that environmental heterogeneity may contribute to the maintenance of GSL variation observed within Arabidopsis thaliana. DOI: http://dx.doi.org/10.7554/eLife.05604.00

Application of Neuroanatomical Ontologies for Neuroimaging Data Annotation

The annotation of functional neuroimaging results for data sharing and re-use is particularly challenging, due to the diversity of terminologies of neuroanatomical structures and cortical parcellation schemes. To address this challenge, we extended the Foundational Model of Anatomy Ontology (FMA) to include cytoarchitectural, Brodmann area labels, and a morphological cortical labeling scheme (e.g., the part of Brodmann area 6 in the left precentral gyrus). This representation was also used to augment the neuroanatomical axis of RadLex, the ontology for clinical imaging. The resulting neuroanatomical ontology contains explicit relationships indicating which brain regions are “part of” which other regions, across cytoarchitectural and morphological labeling schemas. We annotated a large functional neuroimaging dataset with terms from the ontology and applied a reasoning engine to analyze this dataset in conjunction with the ontology, and achieved successful inferences from the most specific level (e.g., how many subjects showed activation in a subpart of the middle frontal gyrus) to more general (how many activations were found in areas connected via a known white matter tract?). In summary, we have produced a neuroanatomical ontology that harmonizes several different terminologies of neuroanatomical structures and cortical parcellation schemes. This neuroanatomical ontology is publicly available as a view of FMA at the Bioportal website1. The ontological encoding of anatomic knowledge can be exploited by computer reasoning engines to make inferences about neuroanatomical relationships described in imaging datasets using different terminologies. This approach could ultimately enable knowledge discovery from large, distributed fMRI studies or medical record mining