3,171 research outputs found
Coordination Geometries in Metallobundles Enforcing Oxidative and Hydrolytic Catalysis and Designing Biomaterials for Use As Antimicrobials
De novo protein design permits discovery of intricate folds and functions emulating natural enzymes in simpler, yet robust model constructs. Helical bundles serve as premier scaffolds to incorporate diverse reactivities from oxidative, reductive, to hydrolytic transformations observed in much grander O2-utilizing metalloproteins such as radical-generating ribonucleotide reductases and catalases. One notable family of de novo proteins is the Due Ferri or DF series of four-helix bundles providing a dinuclear site for metal incorporation and are amenable for tailoring active site reactivity. As reactive oxygen species and radical-based intermediates are prevalent and necessary for steering life-essential processes through reactive radicals stabilized by metals, we were curious to understand how the nature and number of metal ions influence sequestration of such species. We investigated the influence metal has on semiquinone stabilization in DF bundles, a minimalist model representing active sites of more complex natural diiron and dimanganese proteins. Coordination sphere was modified in the original DF single chain version to incorporate a 2-His-1-carboxylate facial triad, a single metal binding motif, mirroring morphology of mononuclear non-heme enzymes. We discovered breaking symmetry of the metal coordination site leads to a stable construct with one site exhibiting tight affinity for metal, and this single metal binding construct Uno Ferro single chain stabilizes semiquinone radical anions equally efficient as a two-metal binding version. We envision a robust and easy to modify DFsc and UFsc family of proteins would be versatile tools for gaining mechanistic insights of metalloenzymes. One application of DF constructs we\u27ve pursued is to create a hydrolase bridging a heteronuclear metallosite. Phosphoester substrates were introduced to DFsc and UFsc to characterize hydrolase features. Defining the structural and functional properties of hydrolases in DF proteins would facilitate creation of catalysts for bioremediation purposes. We further apply minimalist design approaches to redesign natural proteins displaying no inherent catalytic properties (or showing marginal activity) for a chosen chemical transformation. Calmodulin and myoglobin were selected as model proteins to introduce enzymatic properties rationally designed using non-rigorous set of computational tools to modify the substrate pocket for evolution. We use HSQC-NMR to guide the directed evolution process to arrive at beneficial mutations which enhance reactivity of generated enzymes. Our minimalist design approach also demonstrates the practical application of our calmodulin designs to reveal an acid-base promoted catalysis in conversion of therapeutics to their metabolically active forms. Only a single precisely positioned amino acid is needed to promote conversion of an antirheumatic prodrug leflunomide bearing an isoxazole ring for proton abstraction to the active form teriflunomide. Furthermore, we dissected possible defense mechanisms microorganisms utilize to survive habitats under oxidative stress. A reported diiron catalase conserved exclusively in Mycobacterium tuberculosis (Mtb) was characterized to determine if the protein acts as a dimanganese catalase as we observed the coordination ligands are similar to nonheme catalases. Therefore, we sought to identify metal preference of this four-helix bundle and establish possible mechanisms utilized by Mtb to disproportionate toxic oxygen metabolites. Conversely, a possible defense strategy by humans to promote bacterial clearance in cases where invasive bacteria trigger human innate immune responses was examined. Hemoglobin is found to be antimicrobial generating cytotoxic radicals to sustain microbicidal action. We considered myoglobin involved in similar peroxidatic processes could be reactive in presence of pathogen associated molecular patterns, specifically lipopolysaccharides (LPS), to produce radical cations. Hence, myoglobin was characterized in a mixture of different proteases and LPS for peroxidase activation. Lastly, design of antimicrobial hydrogels is described. Our hydrogel design is based on self-assembly of peptides induced by silver or copper complexation and does not incorporate permanent crosslinking agents. Short peptides of alternating polar and nonpolar amino acids affixed by an unnatural amino acid pyridyl alanine which coordinate metal form a strong hydrogel. The hydrogel is self-healing and can be delivered in syringe format for application in wound healing therapy
Sustaining Economic Exploitation of Complex Ecosystems in Computational Models of Coupled Human-Natural Networks
Understanding ecological complexity has stymied scientists for decades. Recent elucidation of the famously coined "devious strategies for stability in enduring natural systems" has opened up a new field of computational analyses of complex ecological networks where the nonlinear dynamics of many interacting species can be more realistically mod-eled and understood. Here, we describe the first extension of this field to include coupled human-natural systems. This extension elucidates new strategies for sustaining extraction of biomass (e.g., fish, forests, fiber) from ecosystems that account for ecological complexity and can pursue multiple goals such as maximizing economic profit, employment and carbon sequestration by ecosystems. Our more realistic modeling of ecosystems helps explain why simpler "maxi-mum sustainable yield" bioeconomic models underpinning much natural resource extraction policy leads to less profit, biomass, and biodiversity than predicted by those simple models. Current research directions of this integrated natu-ral and social science include applying artificial intelligence, cloud computing, and multiplayer online games
Acceptance of a Socially Responsible Label Model for Apparel Products: Application of the Technology Acceptance Model
With a growing group of environmentally and socially conscious consumers, the range of socially responsible (SR) products available in the market has likewise expanded (Marquardt, 2010); currently over 300 different SR labels are being used (Case, 2009). Because such diverse labels exist, consumers have been struggling with identifying information on the label to make an informed, SR purchase decision (D’Souza, 2004; Horne, 2009). In particular, due to the complicated nature of SR practices in apparel products, consumers feel difficulties in identifying SR apparel products and practices in the marketplace (Chen & Burns, 2006; Goswami, 2008)
Who Read Socially Responsible Apparel Labels
Socially responsible (SR) labeling has been developed to encourage consumers to make SR purchases based on ecological attributes of products and additional SR information listed on labels (D’Souza, 2004). Previous research studied the efficacy of SR labels and revealed that SR labels influenced consumers’ purchasing decisions (Dickson, 2001; D’Souza et al., 2007). Despite the fact that SR issues in the apparel industry are significant considerations, practicing conscientious apparel consumption can be challenging for fashion consumers when surrounded by fast fashion and the desire for the latest fashion styles
A Novel Treatment of Postpartum Depression and Review of Literature.
Early-onset postpartum depression has been shown to have a unique neurobiological basis compared to major depressive disorder, implying a need for targeted treatments such as the recent Food and Drug Administration (FDA)-approved brexanolone. In this case report, a woman with a past medical history of major depressive disorder was diagnosed with postpartum depression due to worsening mood with suicidal and homicidal ideations. She was treated with vilazodone and aripiprazole with good effect after consideration of her past medication trials. Her regimen is unique in clinical practice and not reported in current literature for the treatment of postpartum depression. It may represent a safe and effective medication choice, especially in the context of current first-line treatments that have a high treatment failure rate. More research is needed to find treatments that address the unique challenges of postpartum women
The Reciprocal Involvement of Family Business Owners and Communities in Business Success
It is believed that highly involved business owners and community members will yield benefits to ensure business and community sustainability over time. However, little research has delved into understanding the role of business owners’ involvement and the community’s involvement in business outcomes. Thus, the purpose of this study was to investigate the reciprocal involvement of family business owners and the community. To investigate this phenomenon, this study utilized survey data from a rare group of business owners who currently operate long-standing businesses. Results indicate that more involved business owners perceived higher levels of business success. When seeking a profit, business owners also tended to be more involved in the community than owners not seeking a profit. However, family-owned businesses felt that the community did not contribute to their businesses and did not stay involved over time. Overall, business owners felt that they contributed more than the community provided in return. Recommendation is made to stress in entrepreneurship curricula the importance of reciprocal involvement between businesses and their communities and vice versa to promote business and community sustainability over time
The Implementation of Lean Production and Environmental Sustainability Practices in the Indian Apparel Manufacturing Industry
In response to global environmental issues and stiffer business competition, the last few decades have witnessed a tremendous increase in the awareness of environmental impact and the usage of production management systems such as lean production. A focus on reducing adverse impact on the environment has promoted the use of sustainable business practices. Sustainability, which promotes harmonious coexistence of the human race and nature, allows for development without unintended negative consequences on the environment and natural resources (EPA, 2012)
egaku: Enhancing the Sketching Process
Architects sketch using a translucent vellum tracing paper with a thick pencil or marker. The translucency of the paper allows architects to employ a layer-drawing technique for the exploration of ideas derived from their basic design. For example, working with a single base layer such as a map of the site, architects can design upwards of hundreds of possible variations. This ultimately leads to a great pile of drawings, which compose the piles of papers typically strewn about an architecture studio. Individually, these “referential” sketches represent small pieces of a much larger design concept [Graves 1977]. Although they are valuable,they are often cumbersome to manage during the ideation process because it interrupts the flow of ideation, and even difficult to understand when a single sketch is taken out of associated sketches
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