Enzyme responsive surfaces: towards a smart cell-material interface

Enzymes are promising stimuli for the development of responsive biomaterials for biomedical applications. Enzymes are inherently present in the biological environment thus cleverly designed materials for biomedical applications may require no external stimuli to ellicit the required material response. They have been targeted as stimuli in self assembly of bulk materials owing to the material changes in chemical composition afforded by the enzyme interaction. The first examples of autonomous self-regulated drug delivery systems have been reported via the development of reversible enzyme responsive materials that undergo a material change regulated by the enzymes in their environment. Although enzyme responsive surfaces have been reported there are no examples of reversible enzyme response surfaces. The surface is the first point of contact between the biological environment and a biomedical device/implant. Improving this interaction will improve the integration of these biomaterials in biological systems and it has been proposed that biomimetic surfaces are a promising method for full biomaterial integration in the biological environment. The body strives towards homeostasis and this is frequently achieved by enzymatic activating and deactivation of proteins in the body. This process is repeatable and reversible. Herein we address the absence of reversible and repeatable synthetic enzyme responsive surfaces towards the improvement of biomaterial integration. We aim to develop a truly autonomous system wherein enzymes present in the environment can interact with the modified surface to mediate a reversible material response. This goal was achieved by modifying surfaces with copolymers that contain the recognition sequence for Casein kinase II and Alkaline phosphatase to undergo enzymatic phosphorylation and dephosphorylation. Co and homo polymers of serine and glutamic acid were synthesised in solution and conformation/composition relationship was determined by analysis with NMR, GPC and FTIR. Polymerisation from the surface with NCA-Glu and NCA-Ser was achieved as characterised by FTIR, ToF SIMS, XPS and WCA. Enzymatic mediated phosphorylation (CKII) and dephosphorylation (AP) was monitored by surface analysis (ToF SIMS), by monitoring ATP to ADP conversion and phosphate cleavage from the surface using luminescence and colorimetric assays. Conformational changes mediated by enzymatic interactions with the surface was monitored indirectly using a FRET system incorporated in the surface modification. The modified surfaces were able to support cell culture and osteogenesis. This project has made advances in several fields, 1) The use of NCA-ROP as a method to modify surfaces with copolymers, in particular for a random/ alternating amino acid sequence. 2) The use of NCA-ROP as a method to develop stimuli responsive surfaces, specifically, this is the first report of an enzyme responsive surface prepared from NCA-amino acid derivatives. 3) The use of enzymes as stimuli, specifically, this is the first report of a reversible enzymatic responsive surface. In this system reversible phosphorlyation and dephosphorylation was monitored via changes in fluorescence output indicative of induced conformational changes

Cardiomyopathy Following Latrodectus Envenomation

Latrodectus envenomations are common throughout the United States and the world. While many envenomations can result in catecholamine release with resultant hypertension and tachycardia, myocarditis is very rare. We describe a case of a 22-year-old male who sustained a Latrodectus envenomation complicated by cardiomyopathy

Nitrate enrichment does not affect enteropathogenic Escherichia coli in aquatic microcosms but may affect other strains present in aquatic habitats

Eutrophication of the planet’s aquatic systems is increasing at an unprecedented rate. In freshwater systems, nitrate—one of the nutrients responsible for eutrophication—is linked to biodiversity losses and ecosystem degradation. One of the main sources of freshwater nitrate pollution in New Zealand is agriculture. New Zealand’s pastoral farming system relies heavily on the application of chemical fertilisers. These fertilisers in combination with animal urine, also high in nitrogen, result in high rates of nitrogen leaching into adjacent aquatic systems. In addition to nitrogen, livestock waste commonly carries human and animal enteropathogenic bacteria, many of which can survive in freshwater environments. Two strains of enteropathogenic bacteria found in New Zealand cattle, are K99 and Shiga-toxin producing Escherichia coli (STEC). To better understand the effects of ambient nitrate concentrations in the water column on environmental enteropathogenic bacteria survival, a microcosm experiment with three nitrate-nitrogen concentrations (0, 1, and 3 mg NO3-N/L), two enteropathogenic bacterial strains (STEC O26—human, and K99—animal), and two water types (sterile and containing natural microbiota) was run. Both STEC O26 and K99 reached 500 CFU/10 ml in both water types at all three nitrate concentrations within 24 hours and remained at those levels for the full 91 days of the experiment. Although enteropathogenic strains showed no response to water column nitrate concentrations, the survival of background Escherichia coli, imported as part of the in-stream microbiota did, surviving longer in 1 and 3 mg NO3-N/L concentrations (P < 0.001). While further work is needed to fully understand how nitrate enrichment and in-stream microbiota may affect the viability of human and animal pathogens in freshwater systems, it is clear that these two New Zealand strains of STEC O26 and K99 can persist in river water for extended periods alongside some natural microbiota

Analysis of enzyme-responsive peptide surfaces by Raman spectroscopy

We report on the use of Raman spectroscopy as a tool to characterise model peptide functionalised surfaces. By taking advantage of Raman reporters built into the peptide sequence, the enzymatic hydrolysis of these peptides could be determined

External validation of a simple clinical tool used to predict falls in people with Parkinson disease

Published in final edited form as: Parkinsonism Relat Disord. 2015 August ; 21(8): 960–963. doi:10.1016/j.parkreldis.2015.05.008.BACKGROUND: Assessment of fall risk in an individual with Parkinson disease (PD) is a critical yet often time consuming component of patient care. Recently a simple clinical prediction tool based only on fall history in the previous year, freezing of gait in the past month, and gait velocity <1.1 m/s was developed and accurately predicted future falls in a sample of individuals with PD. METHODS: We sought to externally validate the utility of the tool by administering it to a different cohort of 171 individuals with PD. Falls were monitored prospectively for 6 months following predictor assessment. RESULTS: The tool accurately discriminated future fallers from non-fallers (area under the curve [AUC] = 0.83; 95% CI 0.76–0.89), comparable to the developmental study. CONCLUSION: The results validated the utility of the tool for allowing clinicians to quickly and accurately identify an individual's risk of an impending fall.Davis Phinney Foundation, Parkinson Disease Foundation, NIH, APDA. (Davis Phinney Foundation; Parkinson Disease Foundation; NIH; APDA

The Ursinus Weekly, October 23, 1961

Lettinger to lead freshmen; Kelly elected vice-president • Sororities accept sixty new sisters • Two rediscovered works highlight woodwind five\u27s Bomberger performance • Minnich, Weiss win state Young Republican offices • Lawrence calls collegians for press conference: Weekly editor represents Ursinus at Capitol confab • Ursinus to hear Maine\u27s Senator Smith; Receives honorary degree on Founders Day • Efficiency, devotion to duty mark Margaret Chase Smith • Pradervand, Zabarah come to Ursinus from Switzerland, Yemen for studies • President lauds Parents Day; Excellent preparations cited • Editorial: Credit where credit is due • Ursinus in the past • Education by travel • Letters to the editor • 30 yard run breaks Bears backs following 12-6 victory over Wilkes • Hockey lassies remain unbeaten; Defeat Swarthmore, tie Temple girls • Bakermen boot first foes; Lose third tilt to Hens, 2-0 • Hakanson\u27s heft plugs defensive hole; Massachusetts man UC\u27s middle guard • Dean Kellow talks on medical school • Dr. Armstrong organizing second European Tour • German Club members get first-hand Berlin accounthttps://digitalcommons.ursinus.edu/weekly/1301/thumbnail.jp

Tuning the conformation of synthetic co-polypeptides of serine and glutamic acid through control over polymer composition

Ring opening polymerization (ROP) of N‐carboxy anhydride (NCA) amino acids presents a rapid way to synthesize high molecular weight polypeptides with different amino acid compositions. The compositional and functional versatility of polypeptides make these materials an attractive choice for biomaterials. The functional performance of polypeptide materials is equally linked to their conformation which is determined by the amino acid sequence in the polymer chains. Here, the interplay between composition and conformation of synthetic polypeptides obtained by NCA polymerization was explored. Various copolypeptides from Glu(Bzl) and Ser(Bzl) were prepared to investigate how polypeptide composition affected the conformation of the resulting copolymer. Polymerization kinetics indicated that the copolymerization of Glu(Bzl) and Ser(Bzl) preferentially yielded alternating copolymers. Both the polydispersity and the conformation of the polypeptides were dependent on the Ser(Bzl) content in the polymer, demonstrating that polypeptide functionalities could be tuned directly by altering the relative amounts of amino acids in the chain. This work presents the first step toward an improved understanding and control over polypeptide conformation through modulating the amino acid composition of the material. Understanding this sequence–functionality relationship is essential to advancing the use of ROP as a technique to design smart polypeptide based materials with specific functions

Outcomes and care practices for preterm infants born at less than 33 weeks’ gestation: A quality-improvement study

BACKGROUND: Preterm birth is the leading cause of morbidity and mortality in children younger than 5 years. We report the changes in neonatal outcomes and care practices among very preterm infants in Canada over 14 years within a national, collaborative, continuous quality-improvement program. METHODS: We retrospectively studied infants born at 23–32 weeks’ gestation who were admitted to tertiary neonatal intensive care units that participated in the Evidence-based Practice for Improving Quality program in the Canadian Neonatal Network from 2004 to 2017. The primary outcome was survival without major morbidity during the initial hospital admission. We quantified changes using process-control charts in 6-month intervals to identify special-cause variations, adjusted regression models for yearly changes, and interrupted time series analyses. RESULTS: The final study population included 50 831 infants. As a result of practice changes, survival without major morbidity increased significantly (56.6% [669/1183] to 70.9% [1424/2009]; adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 1.06–1.10, per year) across all gestational ages. Survival of infants born at 23–25 weeks’ gestation increased (70.8% [97/137] to 74.5% [219/294]; adjusted OR 1.03, 95% CI 1.02–1.05, per year). Changes in care practices included increased use of antenatal steroids (83.6% [904/1081] to 88.1% [1747/1983]), increased rates of normothermia at admission (44.8% [520/1160] to 67.5% [1316/1951]) and reduced use of pulmonary surfactant (52.8% [625/1183] to 42.7% [857/2009]). INTERPRETATION: Network-wide quality-improvement activities that include better implementation of optimal care practices can yield sustained improvement in survival without morbidity in very preterm infants

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits