Self-assembled peptide template directed synthesis of one-dimensional inorganic nanostructures and their applications

Ankara : The Materials Science and Nanotechnology Program of the Graduate School of Engineering and Sciences of Bilkent University, 2012.Thesis (Ph. D.) -- Bilkent University, 2012.Includes bibliographical references.Engineering at the nano scale has been an active area of science and technology over the last decade. Inspired by nature, synthesis of functional inorganic materials using synthetic organic templates constitutes the theme of this thesis. Developing organic template directed synthesis approach for inorganic nanomaterial synthesis was aimed. For this purpose, an amyloid like peptide sequence which is capable of self-assembling into nanofibers in convenient conditions was designed and decorated with functional groups showing relatively high affinity to special inorganic ions, which are presented at the periphery of the one-dimensional peptide nanofiber. These chemical groups facilitated the deposition of targeted inorganic monomers onto the nanofibers yielding one-dimensional organic-inorganic core-shell nanostructures. The physical and chemical properties of the synthesized peptide nanofibers and inorganic nanostructures were characterized using both qualitative and quantitative methods. First, silica nanotubes were obtained by silica mineralization around these peptide nanofiber templates for the construction of sensors for explosives. The fluorescence dye was used to coat the silica nanotubes to detect explosive vapor. The surface of the silica nanotubes were porous enough to adsorb more dye compared to the silica nanoparticles and silica film, and causes faster fluorescence quenching in the presence of explosives like trinitrotoluene and dinitrotoluene. The silica nanotubes which synthesized with this peptide nanofiber templates can be used in catalysis and sensors in which high surface area is advantageous. In the second part of the thesis, titanium dioxide nanotubes were obtained from titania mineralization. They are wellknown with their fascinating properties as a result of the one-dimensional nanostructure, such as more efficient electron transfer and less electron-hole recombination. The sufficient photoactivity of titanium dioxide makes them suitable materials for Dye-Sensitized Solar-Cell construction. It is demonstrated that the peptide nanofiber templated titanium dioxide nanotubes have more than two times more efficiency compared to template-free synthesized titanium dioxide particles. Finally, designed peptide sequence was conducted to a multi-step seeding mediated growth method for gold mineralization around peptide nanofibers. The gold-peptide hybrid nanostructures with different packing characteristics and sizes were synthesized and fully characterized. Further, it was demonstrated that the dry film of these nanostructures showed a resistive switching dominant conductivity, due to the nanogaps in between gold nanoparticles as a result of particle alignment driven by the peptide nanofiber. The results obtained in this thesis encourage use of a new “bottom-up” synthesis approach. Specially designed peptides with desired properties and functional groups were synthesized and peptide nanofibers formed were further used as templates for inorganic mineralization. Not only it is possible to synthesis high amount of nanostructure with this approach, but also formed one-dimensional nanostructures show advance functionalities used in several applications as a part of the thesis scope. This methodology is suitable for many metals and metal oxide based applications.Acar, HandanPh.D

Natural and Synthetic Biomaterials for Engineering Multicellular Tumor Spheroids

The lack of in vitro models that represent the native tumor microenvironment is a significant challenge for cancer research. Two-dimensional (2D) monolayer culture has long been the standard for in vitro cell-based studies. However, differences between 2D culture and the in vivo environment have led to poor translation of cancer research from in vitro to in vivo models, slowing the progress of the field. Recent advances in three-dimensional (3D) culture have improved the ability of in vitro culture to replicate in vivo conditions. Although 3D cultures still cannot achieve the complexity of the in vivo environment, they can still better replicate the cell–cell and cell–matrix interactions of solid tumors. Multicellular tumor spheroids (MCTS) are three-dimensional (3D) clusters of cells with tumor-like features such as oxygen gradients and drug resistance, and represent an important translational tool for cancer research. Accordingly, natural and synthetic polymers, including collagen, hyaluronic acid, Matrigel®, polyethylene glycol (PEG), alginate and chitosan, have been used to form and study MCTS for improved clinical translatability. This review evaluates the current state of biomaterial-based MCTS formation, including advantages and disadvantages of the different biomaterials and their recent applications to the field of cancer research, with a focus on the past five years.This work is supported in part by the Oklahoma Tobacco Settlement Endowment Trust awarded to the University of Oklahoma, Stephenson Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Oklahoma Tobacco Settlement Endowment Trust. Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Evaluation and Neurodevelopmental Outcomes of Infants with Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia: A Single Center Experience

Hypoxic ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in newborns. Our study aimed to determine the neurodevelopmental outcomes, risk factors, and the relationship between risk factors and prognosis of cases followed up with HIE diagnosis and who were treated with hypothermia treatment. Medical records of 23 patients who were followed up with HIE diagnosis in the pediatric neurology outpatient clinic between January 1, 2018, and December 31, 2021, and treated with therapeutic hypothermia in the newborn period were retrospectively reviewed. Denver Developmental Screening Test II was used in the developmental evaluation. Neurodevelopment was normal in 12 (52.2%) of 23 cases and retarded for age in 11 (47.8%) cases. Variables such as Sarnat encephalopathy score in the neonatal period, need for prolonged ventilation, presence of severe acidosis at birth, Apgar scores at the 1st and 5th minutes, and abnormal cranial magnetic resonance (Mrg) findings were determined to be major factors in determining neurodevelopmental prognosis in asphyxic cases. The male gender was found to be riskier in terms of prognosis. Of the patients with HIE, retardation was determined for fine motor skills in 52.2%, speaking in 39.1%, gross motor skills in 26.1%, and personal development in 21.7%. Epilepsy, cerebral palsy, and speech disorders were the most common chronic period problems in patients with HIE. Despite therapeutic hypothermia treatment, neurodevelopmental problems are still observed in newborns with HIE. We found that male gender, low Apgar score, severe acidosis, and abnormal cranial Mrg findings in the neonatal period are risk factors in determining the neurodevelopmental prognosis of newborns with HIE. Monitoring and supporting the development of HIE cases with risk factors from the first months of life and intervening in developmental problems promptly are crucial in order to improve long-term outcomes

Characterization and quantification of necrotic tissues and morphology in multicellular ovarian cancer tumor spheroids using optical coherence tomography

The three-dimensional (3D) tumor spheroid model is a critical tool for high-throughput ovarian cancer research and anticancer drug development in vitro. However, the 3D structure prevents high-resolution imaging of the inner side of the spheroids. We aim to visualize and characterize 3D morphological and physiological information of the contact multicellular ovarian tumor spheroids growing over time. We intend to further evaluate the distinctive evolutions of the tumor spheroid and necrotic tissue volumes in different cell numbers and determine the most appropriate mathematical model for fitting the growth of tumor spheroids and necrotic tissues. A label-free and noninvasive swept-source optical coherence tomography (SS-OCT) imaging platform was applied to obtain two-dimensional (2D) and 3D morphologies of ovarian tumor spheroids over 18 days. Ovarian tumor spheroids of two different initial cell numbers (5,000- and 50,000- cells) were cultured and imaged (each day) over the time of growth in 18 days. Four mathematical models (Exponential-Linear, Gompertz, logistic, and Boltzmann) were employed to describe the growth kinetics of the tumor spheroids volume and necrotic tissues. Ovarian tumor spheroids have different growth curves with different initial cell numbers and their growths contain different stages with various growth rates over 18 days. The volumes of 50,000-cells spheroids and the corresponding necrotic tissues are larger than that of the 5,000-cells spheroids. The formation of necrotic tissue in 5,000-cells numbers is slower than that in the 50,000-cells ones. Moreover, the Boltzmann model exhibits the best fitting performance for the growth of tumor spheroids and necrotic tissues. Optical coherence tomography (OCT) can serve as a promising imaging modality to visualize and characterize morphological and physiological features of multicellular ovarian tumor spheroids. The Boltzmann model integrating with 3D OCT data of ovarian tumor spheroids provides great potential for high-throughput cancer research in vitro and aiding in drug development.Histology service provided by the Tissue Pathology Shared Resource was supported in part by the National Institute of General Medical Sciences Grant P20GM103639 and National Cancer Institute Grant P30CA225520 of the National Institutes of Health. Research reported in this publication was supported in part by a Stephenson Cancer Center Trainee Research Award funded by the National Cancer Institute Cancer Center Support Grant P30CA225520 awarded to the University of Oklahoma Stephenson Cancer Center. Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria

BackgroundMigraine without aura (MwoA) is a very frequent and remarkable comorbidity in patients with idiopathic/genetic epilepsy (I/GE). Frequently in clinical practice, diagnosis of MwoA may be challenging despite the guidance of current diagnostic criteria of the International Classification of Headache Disorders 3 (ICHD-3). In this study, we aimed to disclose the diagnostic gaps in the diagnosis of comorbid MwoA, using a zone concept, in patients with I/GEs with headaches who were diagnosed by an experienced headache expert.MethodsIn this multicenter study including 809 consecutive patients with a diagnosis of I/GE with or without headache, 163 patients who were diagnosed by an experienced headache expert as having a comorbid MwoA were reevaluated. Eligible patients were divided into three subgroups, namely, full diagnosis, zone I, and zone II according to their status of fulfilling the ICHD-3 criteria. A Classification and Regression Tree (CART) analysis was performed to bring out the meaningful predictors when evaluating patients with I/GEs for MwoA comorbidity, using the variables that were significant in the univariate analysis.ResultsLonger headache duration (<4 h) followed by throbbing pain, higher visual analog scale (VAS) scores, increase of pain by physical activity, nausea/vomiting, and photophobia and/or phonophobia are the main distinguishing clinical characteristics of comorbid MwoA in patients with I/GE, for being classified in the full diagnosis group. Despite being not a part of the main ICHD-3 criteria, the presence of associated symptoms mainly osmophobia and also vertigo/dizziness had the distinguishing capability of being classified into zone subgroups. The most common epilepsy syndromes fulfilling full diagnosis criteria (n = 62) in the CART analysis were 48.39% Juvenile myoclonic epilepsy followed by 25.81% epilepsy with generalized tonic-clonic seizures alone.ConclusionLonger headache duration, throbbing pain, increase of pain by physical activity, photophobia and/or phonophobia, presence of vertigo/dizziness, osmophobia, and higher VAS scores are the main supportive associated factors when applying the ICHD-3 criteria for the comorbid MwoA diagnosis in patients with I/GEs. Evaluating these characteristics could be helpful to close the diagnostic gaps in everyday clinical practice and fasten the diagnostic process of comorbid MwoA in patients with I/GEs

On the issue of transparency and reproducibility in nanomedicine.

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio-nano papers, the community responds

Transient Biocompatible Polymeric Platforms for Long-Term Controlled Release of Therapeutic Proteins and Vaccines

Polymer-based interpenetrating networks (IPNs) with controllable and programmable degradation and release kinetics enable unique opportunities for physisorption and controlled release of therapeutic proteins or vaccines while their chemical and structural integrities are conserved. This paper presents materials, a simple preparation method, and release kinetics of a series of long-term programmable, biocompatible, and biodegradable polymer-based IPN controlled release platforms. Release kinetics of the gp41 protein was controlled over a 30-day period via tuning and altering the chemical structure of the IPN platforms. Post-release analysis confirmed structural conservation of the gp41 protein throughout the process. Cell viability assay confirmed biocompatibility and non-cytotoxicity of the IPNs

Cathepsin B Mediated Cleavage of Peptides

Ofelya Baghdasaryan; Biochemistry; [email protected]. Faculty mentor: Acar Handan; Biomedical Engineering; [email protected]