The development of peptide-based, radiometal-labeled PET imaging agents has seen an increase in attention due to the favorable properties the peptide backbone exhibits. These include high selectivity and affinity to proteins and cells directly linked to various types of cancers. In addition, rapid clearance from circulation and low toxicity allow for unique approaches to engineering a viable peptide-based imaging agent.
View Article and Find Full Text PDFControlling the reduction midpoint potential of heme B is a key factor in many bioelectrochemical reactions, including long-range electron transport. Currently, there are a number of globular model protein systems to study this biophysical parameter; however, there are none for large polymeric protein model systems (e.g.
View Article and Find Full Text PDFBacteriophage λ's CI repressor protein controls a genetic switch between the virus's lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome-collectively referred to as operator sites. However, the minimal level of information needed for CI to recognize and specifically bind these six unique-but-related sequences is unclear. In a previous study, we introduced an algorithm that extracts the minimal direct readout information needed for λ-CI to recognize and bind its six binding sites.
View Article and Find Full Text PDFProtein-DNA binding is of a great interest due to its importance in many biological processes. Previous studies have presented many factors responsible for the recognition and specificity, but understanding the minimal informational requirements for proteins that bind to multiple DNA-sites is still an understudied area of bioinformatics. Here we focus on the hydrogen bonds displayed by the target DNA in the major groove that take part in protein-binding.
View Article and Find Full Text PDFPeptide materials have a wide array of functions, from tissue engineering and surface coatings to catalysis and sensing. Tuning the sequence of amino acids that comprise the peptide modulates peptide functionality, but a small increase in sequence length leads to a dramatic increase in the number of peptide candidates. Traditionally, peptide design is guided by human expertise and intuition and typically yields fewer than ten peptides per study, but these approaches are not easily scalable and are susceptible to human bias.
View Article and Find Full Text PDFOxidoreductases have evolved over millions of years to perform a variety of metabolic tasks crucial for life. Understanding how these tasks are engineered relies on delivering external electron donors or acceptors to initiate electron transfer reactions. This is a challenge.
View Article and Find Full Text PDFIntroduction: Lymphatic complications following vascular procedures involving the groin require prompt treatment to limit morbidity. Several treatments have been described, including conservative management, aspiration, sclerotherapy, and direct lymphatic ligation with or without a muscle flap have been described. To date, there is no data indicating which treatment results in the shortest time to recovery.
View Article and Find Full Text PDFBackground: Complications following vascular procedures involving the groin can lead to significant morbidity. Achieving stable soft tissue coverage over sites of revascularization can help mitigate complications. Prior evidence supports the use of muscle flaps in reoperative groins and in high risk patient populations to reduce postoperative complications.
View Article and Find Full Text PDFDe novo protein design is a powerful methodology used to study natural functions in an artificial-protein context. Since its inception, it has been used to reproduce a plethora of reactions and uncover biophysical principles that are often difficult to extract from direct studies of natural proteins. Natural proteins are capable of assuming a variety of different structures and subsequently binding ligands at impressively high levels of both specificity and affinity.
View Article and Find Full Text PDFFacial feminization surgery is an increasingly performed component of gender affirmation surgery for transgender women. Preoperative facial CT is performed to plan the adjustment of the patient's masculine characteristics to feminine and to plan operative navigation around specific readily identifiable anatomic structures. In the upper face, surgery is performed to reduce the prominence of the brow and increase the nasofrontal angle; the radiology report should indicate the frontal sinus and supraorbital foramen anatomy.
View Article and Find Full Text PDFFacial feminization surgery (FFS) is an increasingly performed component of gender affirmation surgery for transgender women. Preoperative facial CT is performed to plan the adjustment of the patient's masculine characteristics to feminine, and to plan operative navigation around specific readily identifiable anatomic structures. In the upper face, surgery is performed to reduce the prominence of the brow and increase the nasofrontal angle; the radiology report should indicate the frontal sinus and supraorbital foramen anatomy.
View Article and Find Full Text PDFThe Alternative Reading Frame (ARF) protein is a tumor suppressor encoded by the gene in mammals but not lower regenerative vertebrates, and has been previously implicated as a context-sensitive suppressor of regeneration in murine skeletal muscle and humanized ARF-expressing zebrafish fins. This study extends our investigation of the role of ARF in the regeneration of other solid tissues, including the zebrafish heart and the mammalian digit. Heart regeneration after cryoinjury was used to mimic massive myocardial infarction.
View Article and Find Full Text PDFAlthough heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals.
View Article and Find Full Text PDFResistance to multimodal chemotherapy continues to limit the prognosis of acute lymphoblastic leukemia (ALL). This occurs in part through a process called adhesion-mediated drug resistance, which depends on ALL cell adhesion to the stroma through adhesion molecules, including integrins. Integrin α6 has been implicated in minimal residual disease in ALL and in the migration of ALL cells to the central nervous system.
View Article and Find Full Text PDFSelf-assembled peptide micelles and fibers demonstrate unique control over the photophysical properties of the bound, light-activated chromophore, zinc protoporphyrin IX, (PPIX)Zn. Micelles encapsulate either a mixture of uncoordinated and coordinated (PPIX)Zn or all coordinated depending on the ratio of peptide/porphyrin. As the ratio increases toward a 1:1 micelle/porphyrin ratio, providing the chromophore with a discrete coordination environment reminiscent of unstructured proteins, the micelles favor triplet formation.
View Article and Find Full Text PDFTo take peptide materials from predominantly structural to functional assemblies, variations in cofactor binding sites must be engineered and controlled. Here, we have employed the peptide sequence c16-AHX3K3-CO2H where X3 represents the aliphatic structural component of the peptide design that dictates β-sheet formation and upon self-assembly yields a change in the overall microenvironment surrounding the Zn protoporphyrin IX ((PPIX)Zn) binding site. All peptides studied yield β-sheet rich nanofibers highlighting the materials' resiliency to amino acid substitution.
View Article and Find Full Text PDFInvestigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC) pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients.
View Article and Find Full Text PDFThe quest continues for targeted therapies to reduce the morbidity of chemotherapy and to improve the response of resistant leukemia. Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stromal cells triggers intracellular signals that promote cell-adhesion-mediated drug resistance (CAM-DR). Idelalisib, an U.
View Article and Find Full Text PDFLight-harvesting biomaterials are an attractive target in photovoltaics, photocatalysis, and artificial photosynthesis. Through peptide self-assembly, complex nanostructures can be engineered to study the role of chromophore organization during light absorption and energy transport. To this end, we demonstrate the one-dimensional transport of excitons along naturally occurring, light-harvesting, Zn-protoporphyrin IX chromophores within self-assembled peptide-amphiphile nanofibers.
View Article and Find Full Text PDFRotator cuff (RC) tears are frequently complicated by muscle atrophy. Muscle stem cells (MuSCs) repair damaged myofibers following injury, but their role in the prevention or pathogenesis of atrophy following RC tears remains undefined. We hypothesized that the RC MuSC population would be affected by supraspinatus (SS) and infraspinatus (IS) tendon transection (TT) compared to uninjured muscle in a mouse model of RC tear.
View Article and Find Full Text PDFNature guides the flow of electrons in biological systems with the assistance of multi-heme proteins called cytochromes. In an effort to understand natures approach to developing electronic systems, three peptides that are compositionally identical but sequentially distinct have been designed to study the impact of morphology and hydrophobicity on heme coordination and function.
View Article and Find Full Text PDFSelf-assembling peptide materials have gained significant attention, due to well-demonstrated applications, but they are functionally underutilized. To advance their utility, we use noncovalent interactions to incorporate the biological cofactor heme-B for catalysis. Heme-proteins achieve differing functions through structural and coordinative variations.
View Article and Find Full Text PDFNatural selection in photosynthesis has engineered tetrapyrrole based, nanometer scale, light harvesting and energy capture in light-induced charge separation. By designing and creating nanometer scale artificial light harvesting and charge separating proteins, we have the opportunity to reengineer and overcome the limitations of natural selection to extend energy capture to new wavelengths and to tailor efficient systems that better meet human as opposed to cellular energetic needs. While tetrapyrrole cofactor incorporation in natural proteins is complex and often assisted by accessory proteins for cofactor transport and insertion, artificial protein functionalization relies on a practical understanding of the basic physical chemistry of protein and cofactors that drive nanometer scale self-assembly.
View Article and Find Full Text PDFUnderstanding the role of water in governing the kinetics of the self-assembly processes of amphiphilic peptides remains elusive. Here, we use a multistage atomistic-coarse-grained approach, complemented by circular dichroism/infrared spectroscopy and dynamic light scattering experiments to highlight the dual nature of water in driving the self-assembly of peptide amphiphiles (PAs). We show computationally that water cage formation and breakage near the hydrophobic groups control the fusion dynamics and aggregation of PAs in the micellar stage.
View Article and Find Full Text PDFObjectives: To examine the prevalence and correlates of smoking cessation and receiving professional cessation advice among older smokers in Taiwan.
Methods: Cross-sectional data from the 2008-2010 and 2012 Taiwan Adult Smoking Behavior Survey was used to form a sample of 4081 recent active smokers aged 50+, comprising current smokers and former smokers who quit smoking within the past 12months. We examined three outcome variables: quit attempt in the past 12months, successful cessation for at least 3months, and receipt of health professional cessation advice.