Tobramycin-Treated Pseudomonas aeruginosa PA14 Enhances Streptococcus constellatus 7155 Biofilm Formation in a Cystic Fibrosis Model System

Cystic fibrosis (CF) is a human genetic disorder which results in a lung environment that is highly conducive to chronic microbial infection. Over the past decade, deep-sequencing studies have demonstrated that the CF lung can harbor a highly diverse polymicrobial community. We expanded our existing in vitro model of Pseudomonas aeruginosa biofilm formation on CF-derived airway cells to include this broader set of CF airway colonizers to investigate their contributions to CF lung disease, particularly as they relate to the antibiotic response of the population. Using this system, we identified an interspecies interaction between P. aeruginosa, a bacterium associated with declining lung function and worsening disease, and Streptococcus constellatus, a bacterium correlated with the onset of pulmonary exacerbations in CF patients. The growth rate and cytotoxicity of S. constellatus 7155 and P. aeruginosa PA14 were unchanged when grown together as mixed biofilms in the absence of antibiotics. However, the addition of tobramycin, the frontline maintenance therapy antibiotic for individuals with CF, to a mixed biofilm of S. constellatus 7155 and P. aeruginosa PA14 resulted in enhanced S. constellatus biofilm formation. Through a candidate genetic approach, we showed that P. aeruginosa rhamnolipids were reduced upon tobramycin exposure, allowing for S. constellatus 7155 biofilm enhancement, and monorhamnolipids were sufficient to reduce S. constellatus 7155 biofilm viability in the absence of tobramycin. While the findings presented here are specific to a biofilm of S. constellatus 7155 and P. aeruginosa PA14, they highlight the potential of polymicrobial interactions to impact antibiotic tolerance in unanticipated ways

Review of the Constellation Level II Safety, Reliability, and Quality Assurance (SR&QA) Requirements Documents during Participation in the Constellation Level II SR&QA Forum

At the request of the Exploration Systems Mission Directorate (ESMD) and the Constellation Program (CxP) Safety, Reliability; and Quality Assurance (SR&QA) Requirements Director, the NASA Engineering and Safety Center (NESC) participated in the Cx SR&QA Requirements forum. The Requirements Forum was held June 24-26; 2008, at GRC's Plum Brook Facility. The forums purpose was to gather all stakeholders into a focused meeting to help complete the process of refining the CxP to refine its Level II SR&QA requirements or defining project-specific requirements tailoring. Element prime contractors had raised specific questions about the wording and intent of many requirements in areas they felt were driving costs without adding commensurate value. NESC was asked to provide an independent and thorough review of requirements that contractors believed were driving Program costs, by active participation in the forum. This document contains information from the forum

Mechanochromic, Structurally Colored, and Edible Hydrogels Prepared from Hydroxypropyl Cellulose and Gelatin

Abstract: Hydroxypropyl cellulose (HPC) is an edible, cost‐effective and widely used derivative of cellulose. Under lyotropic conditions in water, HPC forms a photonic, liquid crystalline mesophase with an exceptional mechanochromic response. However, due to insufficient physical cross‐linking photonic HPC can flow freely as a viscous liquid, preventing the exploitation of this mechanochromic material in the absence of any external encapsulation or structural confinement. Here this challenge is addressed by mixing HPC and gelatin in water to form a self‐supporting, viscoelastic, and edible supramolecular photonic hydrogel. It is demonstrated that the structural coloration, mechanochromism and non‐Newtonian shear‐thinning behavior of the lyotropic HPC solutions can all be retained into the gel state. Moreover, the rigidity of the HPC‐gel provides a 69% shorter mechanochromic relaxation time back to its initial color when compared to the liquid HPC–water only system, broadening the dynamic color range of HPC by approximately 2.5× in response to a compressive pressure. Finally, the ability to formulate the HPC‐gels in a scalable fashion from only water and “food‐grade” constituents unlocks a wide range of potential applications, from response‑tunable mechanochromic materials and colorant‐free food decoration, to short‐term sensors in, for example, biodegradable “smart labels” for food packaging

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Thoracic CT findings of novel influenza A (H1N1) infection in immunocompromised patients

The goal of this study is to describe the spectrum of initial and follow-up CT findings of novel influenza A (H1N1) infection in a series of immunocompromised patients. Eight immunocompromised patients with documented novel influenza A (H1N1) had CT imaging at our institution between May 2009 and August 2009. A total of 20 CTs (initial and follow-up) were reviewed for the presence, severity, and distribution of the following: ground glass opacity, consolidation, interlobular septal thickening, mosaic perfusion, airway wall thickening, airway dilatation, nodules, cysts, pleural effusion, pericardial effusion, lymphadenopathy, and air trapping. The most common findings were airway thickening/dilatation, peribronchial ground glass opacity, centrilobular nodules, and tree-in-bud opacities. Peripheral consolidation involving the lower lobes was also a common pattern. Findings frequently involved all lobes and were closely associated with either large or small airways. Two patients presented with atypical CT findings including focal lobar consolidation and patchy lower lobe consolidation with soft tissue centrilobular nodules. Most survivors showed near complete resolution of findings within 35 days. CT scans in immunocompromised patients with novel influenza H1N1 commonly show a strong airway predominance of findings or peripheral areas of consolidation involving the lower lobes. A subset of patients with novel influenza A (H1N1) will show findings not typical of viral infection