synthesis-of-keratin-based-nanofiber-for-biomedical-engineering

Synthesis of Keratin-based Nanofiber for Biomedical Engineering

Electrospinning, due to its versatility and potential for applications in various fields, is being frequently used to fabricate nanofibers. Production of ...

North Carolina A&T State University

The Omniscience mechanical valve has been the subject of multiple clinical investigations with variable results, including reports of high complication and reoperation rates.

Results of valve replacement with Omniscience mechanical prostheses.

The mouse is the animal of choice for the study of molecular mechanisms involved in the regulation of cardiovascular morphogenesis and function. Recently, a series of genetically engineered mouse models have been reported (e.g. cGATA6/lacZ, MinK/lacZ knock-in/knock-out, engrailed2/lacZ, Cardiac troponin I/lacZ) that provide new and exciting information on the development of the atrioventricular conduction system (AVCS). On the basis of these and ongoing studies, concepts for the formation of the AVCS are continuously being adjusted. A proper understanding of the normal developmental mechanisms underlying the cardiac remodelling leading to the formation of the AVCS is imperative for the interpretation of cardiac abnormalities, including conduction disturbances, as observed in some genetically perturbed (knockout) mice. In this paper information on murine AVCS development will be integrated with published and unpublished results from studies in other vertebrates, including human and rabbit. We will illustrate that although many pieces of the puzzle still remain to be gathered, the outline of a very complex and critical event in cardiac morphogenesis is slowly emerging. Specifically, we will re-evaluate the concept of the 'primary ring' in the context of the new insights in the development of the AV junction as provided by the respective mouse models described above.

Mouse models for cardiac conduction system development.

We identified a GATA6 gene enhancer that selectively marks the developing atrioventricular conduction system (AVCS) in transgenic mice. This enhancer reads anterior/posterior and medial/lateral positional information early in the cardiogenic programme and remains active in progressively more restricted subsets of heart cells leading up to AVCS formation. Additional experiments will be required to determine if the potential to be recruited into the AVCS is similarly restricted to a subset of myocardial cells early in the cardiogenic programme or if this enhancer can also be activated de novo in cells that initially reside outside this field. We are using several strategies to identify factors that regulate this and other AVCS enhancers and hence govern AVCS function. We are also using this enhancer to make transgenic mice that express Cre, or an inducible form of Cre, to track lineages and to delete floxed genes in the developing or mature AVCS. This Cre/lox approach provides a means to deconstruct complex congenital heart phenotypes that involve the conduction system and to test whether genes are required to form the AVCS or to maintain AVCS function. Lastly, we are exploring strategies to isolate and analyse AVCS cells from normal and affected hearts.

Transcriptional regulation in the mouse atrioventricular conduction system.

The insect steroid hormone 20-hydroxyecdysone works through a ligand-activated nuclear receptor, the ecdysone receptor (EcR), which plays critical roles in insect development and reproduction. The EcR has been exploited to develop insecticides to control pests and gene switches for gene regulation. Recently reported crystal structures of the EcR protein show different but partially overlapping binding cavities for ecdysteroid (ECD) and diacylhydrazine (DAH) ligands, providing an explanation for the differential activity of DAH ligands in insects. 1-Aroyl-4-(arylamino)-1,2,3,4-tetrahydroquinoline (THQ) ligands were recently discovered as ecdysone agonists. Mutagenesis of the EcR (from Choristoneura fumiferana, CfEcR) ligand binding domain followed by screening in a reporter assay led to the identification of CfEcR mutants, which responded well to THQ ligands but poorly to both ECD and DAH ligands. These mutants were further improved by introducing a second mutation, A110P, which was previously reported to cause ECD insensitivity. Testing of these V128F/A110P and V128Y/A110P mutants in a C57BL/6 mouse model coactivator interaction assay and in insect cells showed that this mutant EcR is activated by THQ ligands but not by ECD or DAH ligands. The CfEcR and its V128F/A110P mutant were used to demonstrate simultaneous regulation of two reporter genes using THQ and DAH ligands.

Highly flexible ligand binding pocket of ecdysone receptor: a single amino acid change leads to discrimination between two groups of nonsteroidal ecdysone agonists.

The cGATA-6 gene is flanked by an enhancer that selectively marks the atrioventricular conduction system (AVCS) in transgenic mice. This enhancer reads anterior/posterior and medial/lateral positional information very early in the cardiogenic program and remains active in progressively more restricted regions of primary myocardium leading up to the emergence of a histologically distinct AVCS. We undertook to parse this enhancer to resolve how the respective AVCS-specific transcription program is regulated at the molecular level. We determined that this AVCS enhancer includes a 102 bp module that is sufficient to restrict expression to primary nonchamber myocardium. This offers a novel tool to analyze the early molecular delineation of primary and chamber myocardium, which subsequently give rise to components of the central and peripheral conduction system, respectively. Furthermore, we show that this 102 bp module in turn contains a nested 47 bp core module that has the potential to direct expression specifically to the AVCS domain of primary myocardium, albeit with low efficiency. Accordingly, we show that a GATA site and a GC-rich site in the 102 bp region bolster the activity of the nested 47 bp AVCS core region even within the context of the parental 1,478 bp enhancer. These are the first functional elements to be reported for a cardiac conduction system-specific control region.

GATA-6 gene enhancer contains nested regulatory modules for primary myocardium and the embedded nascent atrioventricular conduction system.

Preoperative administration of PDE-5 Inhibitors.

False confidences in preoperative pregnancy testing.

This study examined outcomes of endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) using general, spinal, epidural, and local/monitored anesthesia care (MAC) in a multicenter North American hospital database reflecting contemporary anesthesia and surgical practices.

Results of endovascular aortic aneurysm repair with general, regional, and local/monitored anesthesia care in the American College of Surgeons National Surgical Quality Improvement Program database.

PKS biocatalysis: The terminal module of erythromycin synthase was used for the in vitro production of chiral triketide lactones. Combining cofactor regeneration, substrate truncation, and enzymatic promiscuity afforded a scalable strategy to generate these molecules from abundant racemic and achiral precursors. The described biocatalytic platform thus facilitates the application and study of enzymes within PKS modules.

Preparative, in vitro biocatalysis of triketide lactone chiral building blocks.

Keratin-based composite nanofibers have been fabricated by an electrospinning technique. Aqueous soluble keratin extracted from human hair was successfully blended with poly(ε-caprolactone) (PCL) in different ratios and transformed into nanofibrous membranes. Toward the potential use of this nanofibrous membrane in tissue engineering, its physicochemical properties, such as morphology, mechanical strength, crystallinity, chemical structure, and integrity in aqueous medium were studied and its cellular compatibility was determined. Nanofibrous membranes with PCL/keratin ratios from 100/00 to 70/30 showed good uniformity in fiber morphology and suitable mechanical properties, and retained the integrity of their fibrous structure in buffered solutions. Experimental results, using cell viability assays and scanning electron microscopy imaging, showed that the nanofibrous membranes supported 3T3 cell viability. The ability to produce blended nanofibers from protein and synthetic polymers represents a significant advancement in development of composite materials with structural and material properties that will support biomedical applications. This provides new nanofibrous materials for applications in tissue engineering and regenerative medicine.

Angela Edwards

Department of Chemical,
Biological and Bioengineering,
Department of Chemical, Biological and Bioengineering

North Carolina A&T State University

Synthesis of Keratin-based Nanofiber for Biomedical Engineering

Angela Edwards

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Chemical,Biological and Bioengineering,Department of Chemical, Biological and Bioengineering

North Carolina A&T State University

Synthesis of Keratin-based Nanofiber for Biomedical Engineering

Department of Chemical,
Biological and Bioengineering,
Department of Chemical, Biological and Bioengineering