Testing the Viability of Coiled Coils as Biomaterials for Future Use in Regenerative Medicine Applications

Regenerative medicine and some drug delivery today uses natural biomaterials such as collagen and fibrin as platforms on which to attach cells, growth factors, and other biological chemicals, but these can have immunological effects on the body. Developing other biomaterials that can perform the same tasks without the immunological effects would be beneficial to the field as a whole1. This study aimed to recreate known behaviors of collagen fibers using a novel trimeric coiled coil by coordinating the coiled coils into hollow spheres around a metal ion. These spheres could have future use as a drug delivery platform or transport material without the effects of collagen. The peptides used to form the coiled coils were produced using standard solid phase peptide synthesis methods. Three bipyridine molecules were added to each peptide, resulting in nine bipyridines on each coiled coil. Once purified by reverse phase HPLC, metal ions will be added to the coiled coils in an aqueous environment and induced to form structures by stirring and other methods. Shape data will be collected using scanning electron microscopy (SEM) and atomic force microscopy (AFM), while size will be determined using dynamic light scattering (DLS). Preliminary results are expected to show that small hollow spheres were formed, indicating that coiled coils may become a significant part of drug delivery and aspects of regenerative medicine. Further research is needed to determine the full capabilities of coiled coils to transport biomaterials and/or to form scaffolds or other materials related to regenerative medicine

Formation of Microcages from a Collagen Mimetic Peptide via Metal-Ligand Interactions

Here, the hierarchical assembly of a collagen mimetic peptide (CMP) displaying four bipyridine moieties is described. The CMP was capable of forming triple helices followed by self-assembly into disks and domes. Treatment of these disks and domes with metal ions such as Fe(II), Cu(II), Zn(II), Co(II), and Ru(III) triggered the formation of microcages, and micron-sized cup-like structures. Mechanistic studies suggest that the formation of the microcages proceeds from the disks and domes in a metal-dependent fashion. Fluorescently-labeled dextrans were encapsulated within the cages and displayed a time-dependent release using thermal conditions

Potential Tools for Eradicating HIV Reservoirs in the Brain: Development of Trojan Horse Prodrugs for the Inhibition of P-Glycoprotein with Anti-HIV-1 Activity

Combination antiretroviral therapy is the mainstay of HIV treatment, lowering plasma viral levels below detection. However, eradication of HIV is a major challenge due to cellular and anatomical viral reservoirs that are often protected from treatment by efflux transporters, such as P-glycoprotein (P-gp) at the blood–brain barrier (BBB). Herein we described a Trojan horse approach to therapeutic evasion of P-gp based on a reversibly linked combination of HIV reverse transcriptase and protease inhibitors. Potent inhibition of P-gp efflux in cells, including human brain endothelial cells, was observed with the linked heterodimeric compounds. In vitro regeneration of active monomeric drugs was observed in a reducing environment with these dimeric prodrugs, with the superior leaving group promoting more facile release from the tether. These release trends were mirrored in the efficacy of the in cyto anti-HIV-1 activity of the Trojan horse heterodimers

Bridges over troubled waters: an interdisciplinary framework for evaluating the interconnectedness within fragmented domestic flood risk management systems

Diversification of strategies in Flood Risk Management (FRM) is widely regarded as a necessary step forward in terms of lessening the likelihood and magnitude of flooding, as well as minimizing the exposure of people and property, and in turn the disruption, economic damage, health impacts and other adverse consequences that ensue when floods occur. Thus, diversification is often heralded as an essential condition for enhancing societal resilience to flooding. However, an inevitable consequence of diversifying strategies and practices in FRM is that it can lead to fragmentation within FRM systems, in terms of the distribution of responsibilities between actors and governing rules enacted within different policy domains. This can prove detrimental to the effectiveness of FRM. Building upon the notion of fragmentation developed in legal and governance literature, this paper introduces the concept of ‘bridging mechanisms’, i.e. instruments that remedy fragmentation by enhancing interconnectedness between relevant actors through information transfer, coordination and cooperation. This paper develops a typology of both fragmentation and bridging mechanisms and analyzes their relations, partly drawing upon empirical research conducted within the EU ‘STAR-FLOOD’ project. In turn, this paper outlines a novel interdisciplinary methodological framework for evaluating the degree and quality of the interconnectedness within fragmented domestic FRM systems. A pragmatic, flexible and broadly applicable tool, this framework is both suited for academic purposes, as well as for practically oriented analysis and (re)development of fragmented FRM systems, and potentially other fragmented systems, within the EU and abroad

Impact of changing climate on bryophyte contributions to terrestrial water, carbon, and nitrogen cycles

Bryophytes, including the lineages of mosses, liverworts, and hornworts, are the second-largest photoautotroph group on Earth. Recent work across terrestrial ecosystems has highlighted how bryophytes retain and control water, fix substantial amounts of carbon (C), and contribute to nitrogen (N) cycles in forests (boreal, temperate, and tropical), tundra, peatlands, grasslands, and deserts. Understanding how changing climate affects bryophyte contributions to global cycles in different ecosystems is of primary importance. However, because of their small physical size, bryophytes have been largely ignored in research on water, C, and N cycles at global scales. Here, we review the literature on how bryophytes influence global biogeochemical cycles, and we highlight that while some aspects of global change represent critical tipping points for survival, bryophytes may also buffer many ecosystems from change due to their capacity for water, C, and N uptake and storage. However, as the thresholds of resistance of bryophytes to temperature and precipitation regime changes are mostly unknown, it is challenging to predict how long this buffering capacity will remain functional. Furthermore, as ecosystems shift their global distribution in response to changing climate, the size of different bryophyte-influenced biomes will change, resulting in shifts in the magnitude of bryophyte impacts on global ecosystem functions

PlasmoDraft: a database of Plasmodium falciparum gene function predictions based on postgenomic data

<p>Abstract</p> <p>Background</p> <p>Of the 5 484 predicted proteins of <it>Plasmodium falciparum</it>, the main causative agent of malaria, about 60% do not have sufficient sequence similarity with proteins in other organisms to warrant provision of functional assignments. Non-homology methods are thus needed to obtain functional clues for these uncharacterized genes.</p> <p>Results</p> <p>We present PlasmoDraft <url>http://atgc.lirmm.fr/PlasmoDraft/</url>, a database of Gene Ontology (GO) annotation predictions for <it>P. falciparum </it>genes based on postgenomic data. Predictions of PlasmoDraft are achieved with a <it>Guilt By Association </it>method named Gonna. This involves (1) a predictor that proposes GO annotations for a gene based on the similarity of its profile (measured with transcriptome, proteome or interactome data) with genes already annotated by GeneDB; (2) a procedure that estimates the confidence of the predictions achieved with each data source; (3) a procedure that combines all data sources to provide a global summary and confidence estimate of the predictions. Gonna has been applied to all <it>P. falciparum </it>genes using most publicly available transcriptome, proteome and interactome data sources. Gonna provides predictions for numerous genes without any annotations. For example, 2 434 genes without any annotations in the Biological Process ontology are associated with specific GO terms (<it>e.g</it>. Rosetting, Antigenic variation), and among these, 841 have confidence values above 50%. In the Cellular Component and Molecular Function ontologies, 1 905 and 1 540 uncharacterized genes are associated with specific GO terms, respectively (740 and 329 with confidence value above 50%).</p> <p>Conclusion</p> <p>All predictions along with their confidence values have been compiled in PlasmoDraft, which thus provides an extensive database of GO annotation predictions that can be achieved with these data sources. The database can be accessed in different ways. A global view allows for a quick inspection of the GO terms that are predicted with high confidence, depending on the various data sources. A gene view and a GO term view allow for the search of potential GO terms attached to a given gene, and genes that potentially belong to a given GO term.</p

Metal-Promoted Assembly of Two Collagen Mimetic Peptides into a Biofunctional “Spiraled Horn” Scaffold

Biofunctional scaffolds for the delivery of living cells are of the utmost importance for regenerative medicine. Herein, a novel, robust “spiraled horn” scaffold was elucidated through the Co2+-promoted hierarchical assembly of two collagen mimetic peptides, NCoH and HisCol. Each “horn” displayed a periodic banding pattern with band lengths corresponding to the length of the collagen peptide triple helix. Strand exchange between the two peptide trimers resulted in failure to form this intricate morphology, lending support to a precise metal-ligand-based mechanism of assembly. Little change occurred to the observed morphology when the Co2+ concentration was varied from 0.5 to 4.0 mM, and the scaffold was found to be fully formed within two minutes of exposure to the metal ion. The horned network also displayed biological functionality by binding to a His-tagged fluorophore and associating with cells