scholarly journals Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules

Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1342 ◽  
Author(s):  
Aaron Alford ◽  
Brenna Tucker ◽  
Veronika Kozlovskaya ◽  
Jun Chen ◽  
Nirzari Gupta ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Defense Mechanisms ◽  
The Body ◽  
Stimuli Responsive ◽  
Triggered Release ◽  
Quadruplex Dna ◽  
Nucleic Acid Therapeutics ◽  
Wide Range ◽  
G Quadruplex ◽  
Hydrogel Capsules

Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)n multilayer hydrogel capsules loaded with ~7 kDa G-quadruplex DNA. The capsules are shown to release their DNA cargo on demand in response to both enzymatic and ultrasound (US)-triggered degradation. The unique structure adopted by the G-quadruplex is essential to its biological function and we show that the controlled release from the microcapsules preserves the basket conformation of the oligonucleotide used in our studies. We also show that the (PMAA/PVPON) multilayer hydrogel capsules can encapsulate and release ~450 kDa double stranded DNA. The encapsulation and release approaches for both oligonucleotides in multilayer hydrogel microcapsules developed here can be applied to create methodologies for new therapeutic strategies involving the controlled delivery of sensitive biomolecules. Our study provides a promising methodology for the design of effective carriers for DNA vaccines and medicines for a wide range of immunotherapies, cancer therapy and/or tissue regeneration therapies in the future.

scholarly journals A short peptide that preferentially binds c-MYC G-quadruplex DNA

2020 ◽  
Vol 56 (63) ◽  
pp. 8940-8943 ◽  
Author(s):  
Aisling Minard ◽  
Danielle Morgan ◽  
Federica Raguseo ◽  
Anna Di Porzio ◽  
Denise Liano ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Human Genome ◽  
Promoter Region ◽  
Secondary Structures ◽  
Quadruplex Dna ◽  
Short Peptide ◽  
G Quadruplex

G-quadruplexes are nucleic-acids secondary structures that are highly abundant in the human genome. In this work,we identified a short-peptide that displays selectivity for the G-quadruplex formed in the promoter region of the oncogene c-MYC.

scholarly journals Defensive Functioning of Individuals Diagnosed With Gender Dysphoria at the Beginning of Their Hormonal Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Guido Giovanardi ◽  
Marta Mirabella ◽  
Mariagrazia Di Giuseppe ◽  
Francesco Lombardo ◽  
Anna Maria Speranza ◽  
...  
Keyword(s):  
Gender Dysphoria ◽  
Defense Mechanisms ◽  
Rating Scales ◽  
Hormonal Treatment ◽  
The Body ◽  
Assessment Procedure ◽  
Transgender People ◽  
Defensive Functioning ◽  
Wide Range ◽  
Body Uneasiness

Defense mechanisms are relevant indicators of psychological functioning and vulnerability to psychopathology. Their evaluation can unveil individuals' unconscious strategies for mediating reactions to emotional conflict and external stressors. At the beginning of their journey toward gender reassignment, individuals diagnosed with gender dysphoria (GD) may experience conflict and stressful experiences that trigger a wide range of defense mechanisms. Mature defenses may strengthen these individuals as they travel along this important path, while neurotic and immature defenses may exacerbate their body dissatisfaction (BD) and hinder their processing of change. Only a few studies have investigated self-reported defensive functioning in transgender people, finding a higher frequency of maladaptive defense mechanisms relative to controls. The present study was the first to apply an in-depth clinician-rated tool to assess the entire hierarchy of defense mechanisms within a sample of transgender people. Defensive functioning and personality organization were assessed in 36 individuals diagnosed with GD (14 trans women, 22 trans men, mean age 23.47 years), using the Defense Mechanisms Rating Scales (Perry, 1990) and the Shedler-Westen Assessment Procedure-200 (Shedler et al., 2014). Body uneasiness was assessed using the Body Uneasiness Test (BUT; Cuzzolaro et al., 2006). The findings showed that defensive functioning correlated positively with healthy personality functioning and negatively with BD. Compared to cisgender controls, participants with GD who presented greater defensive functioning were found to be more immature and to demonstrate significant differences in many levels of functioning. The clinical implications of the results suggest that psychological interventions aimed at improving defensive functioning in individuals with GD will be important in helping them manage the challenges posed by their gender transition.

scholarly journals Transcriptome Analysis Reveals the Potential Antioxidant Defense Mechanisms of Myzus persicae in Response to UV-B Stress

2019 ◽  
Author(s):  
Changli Yang ◽  
Changyu Zhang ◽  
Jianyu Meng ◽  
Mengshuang Yao
Keyword(s):  
Environmental Stress ◽  
Myzus Persicae ◽  
Defense Mechanisms ◽  
Molecular Mechanisms ◽  
Light Emitting Diode ◽  
Enrichment Analysis ◽  
Membrane Lipid ◽  
The Body ◽  
Ultraviolet B ◽  
Wide Range

Abstract Background: As an environmental stress factor, ultraviolet-B (UV-B) radiation directly affects the growth and development of Myzus persicae. Excessive UV-B stress leads to DNA, membrane lipid, and protein damage by the production of reactive oxygen species. However, M. persicae can adaptively respond to such environmental stress by activating the relevant mechanisms in the body. How M. persicae responds to UV-B stress and the molecular mechanisms underlying this adaptation remain unknown. Results: Here, we compared and analyzed transcriptome data for M. persicae following exposure to a light-emitting diode fluorescent lamp and UV-B radiation for 30 min. We identified 758 significant differentially expressed genes (DEGs) following exposure to UV-B stress, including 423 upregulated and 335 downregulated genes. In addition, enrichment analysis using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases illustrated that these DEGs are associated with antioxidation and detoxification, metabolic and protein turnover, immune response, and stress signal transduction. Simultaneously, these DEGs are closely related to the adaptability to UV-B stress.Conclusions: Our results suggest that UV-B stress is associated with a wide range of physiological effects in M. persicae. Our research can raise awareness of the mechanisms of insect responses to UV-B stress.

scholarly journals pH- and ligand-induced release of loads from DNA–acrylamide hydrogel microcapsules

2017 ◽  
Vol 8 (5) ◽  
pp. 3362-3373 ◽  
Author(s):  
Wei-Ching Liao ◽  
Sivan Lilienthal ◽  
Jason S. Kahn ◽  
Marianna Riutin ◽  
Yang Sung Sohn ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Stimuli Responsive ◽  
Triggered Release

A generic method of preparing stimuli-responsive substrate-loaded hydrogel microcapsules, composed of polyacrylamide chains cross-linked by nucleic acids, has been described. The triggered release of loads from the microcapsules proceeds via either the formation of an ATP aptamer or a cocaine aptamer, or the pH-induced generation of i-motif structures.

A short overview of vitamin C and selected cells of the immune system

Open Medicine ◽  
2011 ◽  
Vol 6 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Voja Pavlovic ◽  
M. Sarac
Keyword(s):  
Immune System ◽  
Vitamin C ◽  
Defense Mechanisms ◽  
Molecular Mechanisms ◽  
The Body ◽  
Water Soluble ◽  
Toxicological Effects ◽  
Positive Effects ◽  
Wide Range ◽  
Vitamin C Supplementation

AbstractVitamin C (ascorbic acid) is an essential water-soluble nutrient that primarily exerts its effect on a host defense mechanisms and immune homeostasis and is the most important physiological antioxidant. Stable intake of vitamin C is essential for life in humans because the body does not synthesize it. Even the numerous studies have demonstrated that vitamin C supplementation stimulates the immune system, prevents DNA damage and significantly decreases the risk of a wide range of pathologies; the potential protective mechanisms are still largely unknown. This review summarizes the recently known facts about the role of vitamin C on the selected cells of the immune system and potential molecular mechanisms involved. Further, in this review, many new data about the positive effects of vitamin C on the immune system, potential toxicological effects, vitamin C supplementation in disease development, as well as some proposed mechanisms of vitamin C activity, are discussed.

scholarly journals Imidazole-modified G-quadruplex DNA as metal-triggered peroxidase

2019 ◽  
Vol 10 (8) ◽  
pp. 2513-2518 ◽  
Author(s):  
Philip M. Punt ◽  
Guido H. Clever
Keyword(s):  
Transition Metals ◽  
Stimuli Responsive ◽  
Peroxidase Mimic ◽  
Quadruplex Dna ◽  
G Quadruplex

Imidazole-modified G-quadruplex DNA binds transition metals Cu(ii), Zn(ii), Ni(ii) and Co(ii). Metal-triggered association with hemin generates a stimuli-responsive peroxidase mimic.

Creating the Wind

2020 ◽  
Vol 2 (4) ◽  
pp. 14-31
Author(s):  
Élodie Dupey García
Keyword(s):  
Indigenous Communities ◽  
The Body ◽  
Historical Sources ◽  
Natural Behavior ◽  
Sensory Experiences ◽  
Identity And Agency ◽  
Wide Range ◽  
Late Postclassic ◽  
Comparative Examination ◽  
Meteorological Phenomenon

This article explores how the Nahua of late Postclassic Mesoamerica (1200–1521 CE) created living and material embodiments of their wind god constructed on the basis of sensory experiences that shaped their conception of this divinized meteorological phenomenon. In this process, they employed chromatic and design devices, based on a wide range of natural elements, to add several layers of meaning to the human, painted, and sculpted supports dressed in the god’s insignia. Through a comparative examination of pre-Columbian visual production—especially codices and sculptures—historical sources mainly written in Nahuatl during the viceregal period, and ethnographic data on indigenous communities in modern Mexico, my analysis targets the body paint and shell jewelry of the anthropomorphic “images” of the wind god, along with the Feathered Serpent and the monkey-inspired embodiments of the deity. This study identifies the centrality of other human senses beyond sight in the conception of the wind god and the making of its earthly manifestations. Constructing these deity “images” was tantamount to creating the wind because they were intended to be visual replicas of the wind’s natural behavior. At the same time, they referred to the identity and agency of the wind god in myths and rituals.

Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators

2020 ◽  
Vol 27 (1) ◽  
pp. 154-169 ◽  
Author(s):  
Claudiu N. Lungu ◽  
Bogdan Ionel Bratanovici ◽  
Maria Mirabela Grigore ◽  
Vasilichia Antoci ◽  
Ionel I. Mangalagiu
Keyword(s):  
Experimental Data ◽  
Antimicrobial Properties ◽  
Qsar Model ◽  
Therapeutic Effectiveness ◽  
Computational Results ◽  
Pyridine Derivatives ◽  
Quadruplex Dna ◽  
Dna Intercalators ◽  
Structure Activity ◽  
G Quadruplex

Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

Emerging Role of G-quadruplex DNA as Target in Anticancer Therapy

2017 ◽  
Vol 22 (44) ◽  
pp. 6612-6624 ◽  
Author(s):  
Graziella Cimino-Reale ◽  
Nadia Zaffaroni ◽  
Marco Folini
Keyword(s):  
Anticancer Therapy ◽  
Quadruplex Dna ◽  
G Quadruplex

scholarly journals The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus

2021 ◽  
Vol 22 (5) ◽  
pp. 2409
Author(s):  
Anastasia A. Bizyaeva ◽  
Dmitry A. Bunin ◽  
Valeria L. Moiseenko ◽  
Alexandra S. Gambaryan ◽  
Sonja Balk ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Core Structure ◽  
Dna Aptamer ◽  
Tertiary Structures ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Flanking Sequences ◽  
Related Proteins

Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5′- and 3′-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385–hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer.

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