The Next Catalyst for Change: How Corporate Shared Value is Reshaping Capitalism

Both corporations and their global conglomerates are looking into the face of an evolving idea of capitalism. As businesses become more intertwined with society, this special relationship is becoming increasingly deterministic of the condition of the world. This paper explores the possibility that if businesses integrate shared value -- a way to combine economic and social value -- into their long-term business plans, that not only will society be better off, but the businesses themselves may be able to explore previously unrecognized potential for profits

Purification of flavan-3-ol biosynthesis for co-localization onto nanocarriers and a multi-enzyme assay

Flavonoids are polyphenolic secondary metabolites that serve a variety of purposes, from assisting pollination in plants to providing anti-cancerous activity in humans. It is the wide range of functions that give these molecules the highly revered status they have today. Range in function can be linked with the range in structure, and with over 10,000 different flavonoids known, they make up one of the largest groups of natural products. One common sub-class of flavonoids is the flavan-3-ols, which are known for their health benefits and tendency to condense to form proanthocyanidins, or condensed tannins. Both of these classes of flavonoids represent the valuable end products of a highly investigated, yet still not fully understood, section of flavonoid biosynthesis. Furthermore, some of the intermediates are highly unstable and have never been isolated in planta. The enzymes that comprise this section are highly interconnected and regulated, suggesting that a possible multi-enzyme complex exists. With this evidence, we propose to create a synthetic complex using a polymer nanocarrier using anthocyanidin synthase and reductase (ANS and ANR, respectively), the final two enzymes in flavan-3-ol biosynthesis. Along with the preceding enzyme, dihydroflavonol 4-reductase (DFR), they have been separately and recombinantly expressed in E. coli. Both ANR and ANS are fused to a specific tag for binding to the nanocarrier, ANR - 6xHis and ANS - (monomeric) streptavidin. Specifying binding sites will allow adjustable enzyme concentration and distribution on the nanocarrier. DFR, which has a stable substrate, allows for generation of the highly unstable ANS substrate. All three enzymes have been designed and purified for co-localization on the nanocarrier and all have exhibited activity in an assay designed for the multi-enzyme reaction

Skin regeneration with a synthetic biomaterial that replaces the extracellular matrix

Our extracellular matrix replacement (EMR) is a photopolymerized, polysaccharide-PEG hydrogel scaffold that promotes functional skin regeneration and stimulates wound closure with reduced scarring. The advanced wound care market is dominated by collagen-based products isolated from animal and human tissues, and these products are often costly, show only modest efficacy, and cannot be extensively modified to provide customized devices. Preclinical data indicates that the EMR provides the optimal mechanical and chemical properties to stimulate an effective and efficient inflammatory response, followed by regeneration of a robust vascular network and restoration of a complete reticulated epithelium, hair follicles, and sebaceous glands. The EMR is a biodegradable synthetic biomaterial, and its properties can be rationally modified by adjusting the reaction conditions under which it is produced. Therefore, future generations of EMR products can be tailored to specific wound types and/or loaded with growth factors and small molecules. We will review EMR discovery and development, covering its synthesis and chemical and biochemical characterization. We will present data from our preclinical animal studies in murine and porcine third degree burn and excisional wound models. Finally, we will discuss efforts to develop scalable EMR manufacturing processes and highlight some future directions to develop next generation EMR-based products

Taxonomic Classification of Bacterial 16S rRNA Genes Using Short Sequencing Reads: Evaluation of Effective Study Designs

Massively parallel high throughput sequencing technologies allow us to interrogate the microbial composition of biological samples at unprecedented resolution. The typical approach is to perform high-throughout sequencing of 16S rRNA genes, which are then taxonomically classified based on similarity to known sequences in existing databases. Current technologies cause a predicament though, because although they enable deep coverage of samples, they are limited in the length of sequence they can produce. As a result, high-throughout studies of microbial communities often do not sequence the entire 16S rRNA gene. The challenge is to obtain reliable representation of bacterial communities through taxonomic classification of short 16S rRNA gene sequences. In this study we explored properties of different study designs and developed specific recommendations for effective use of short-read sequencing technologies for the purpose of interrogating bacterial communities, with a focus on classification using naïve Bayesian classifiers. To assess precision and coverage of each design, we used a collection of ∼8,500 manually curated 16S rRNA gene sequences from cultured bacteria and a set of over one million bacterial 16S rRNA gene sequences retrieved from environmental samples, respectively. We also tested different configurations of taxonomic classification approaches using short read sequencing data, and provide recommendations for optimal choice of the relevant parameters. We conclude that with a judicious selection of the sequenced region and the corresponding choice of a suitable training set for taxonomic classification, it is possible to explore bacterial communities at great depth using current technologies, with only a minimal loss of taxonomic resolution.</p

Functional Characterization and Evolution of the Isotuberculosinol Operon in Mycobacterium Tuberculosis and Related Mycobacteria

Terpenoid metabolites are important to the cellular function, structural integrity, and pathogenesis of the human-specific pathogen Mycobacterium tuberculosis (Mtb). Genetic and biochemical investigations have indicated a role for the diterpenoid isotuberculosinol (isoTb) early in the infection process. There are only two genes (Rv3377c and Rv3378c) required for production of isoTb, yet these are found in what appears to be a five-gene terpenoid/isoprenoid biosynthetic operon. Of the three remaining genes (Rv3379c, Rv3382c, and Rv3383c), previous work has indicated that Rv3379c is an inactive pseudo-gene. Here we demonstrate that Rv3382c and Rv3383c encode biochemically redundant machinery for isoprenoid metabolism, encoding a functional 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB) for isoprenoid precursor production and a geranylgeranyl diphosphate (GGPP) synthase, respectively, for which the Mtb genome contains other functional isozymes (Rv1110 and Rv0562, respectively). These results complete the characterization of the isoTb biosynthetic operon, as well as further elucidating isoprenoid metabolism in Mtb. In addition, we have investigated the evolutionary origin of this operon, revealing Mtb-specific conservation of the diterpene synthase genes responsible for isoTb biosynthesis, which supports our previously advanced hypothesis that isoTb acts as a human-specific pathogenic metabolite and is consistent with the human host specificity of Mtb. Intriguingly, our results revealed that many mycobacteria contain orthologs for both Rv3383c and Rv0562, suggesting a potentially important role for these functionally redundant GGPP synthases in the evolution of terpenoid/isoprenoid metabolism in the mycobacteria

Implementation of Endotracheal Tube Cuff Manometry in the Operating Room: A Quality Improvement Project

Background and Review of Literature: Endotracheal tube cuff pressure should be maintained between 20 to 30 cmH2O to prevent adverse airway outcomes. Standardized practice is not endorsed by any major anesthesia organization nor by Washington University School of Medicine’s Department of Anesthesia. The common practice of manual palpation is unreliable. Use of a manometer is effective to measure and achieve appropriate cuff pressure. Purpose: Implement a quality improvement project to increase the proportion of anesthesia providers using syringe manometers. Methods: The facility’s EHR was used to obtain data reports on AG Cuffill syringe manometer use and documentation at specific time points. The independent variable was staff educational in-services; the dependent variable was the proportion of documented ETT cuff pressures in the EHR. Implementation Plan/Procedure: This quality improvement project consisted of pre-intervention, implementation, and post-intervention phases. Educational in-services were provided two days a week for two weeks at the start of the intervention phase. The in-services aimed to improve provider knowledge and familiarity with syringe manometer use as well as appropriate documentation. Implications/Conclusion: Educational in-services increased the proportion of providers who used and documented syringe cuff manometry. Improved provider adherence may eventually lead to implementation of an established departmental practice for all anesthetics delivered with a cuffed ETT to improve patient outcomes

Host genetic variation in mucosal immunity pathways influences the upper airway microbiome

Nasal microbiome alpha diversity (XLSX 43 kb