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Статті в журналах з теми "Endogenous nucleic acids":
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Kontaki, Elena, and Dimitrios T. Boumpas. "Innate immunity in systemic lupus erythematosus: Sensing endogenous nucleic acids." Journal of Autoimmunity 35, no. 3 (November 2010): 206–11. http://dx.doi.org/10.1016/j.jaut.2010.06.009.
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Roers, Axel, Björn Hiller, and Veit Hornung. "Recognition of Endogenous Nucleic Acids by the Innate Immune System." Immunity 44, no. 4 (April 2016): 739–54. http://dx.doi.org/10.1016/j.immuni.2016.04.002.
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Traykovska, Martina, Sjoerd Miedema, and Robert Penchovsky. "Clinical Trials of Functional Nucleic Acids." International Journal of Biomedical and Clinical Engineering 7, no. 2 (July 2018): 46–60. http://dx.doi.org/10.4018/ijbce.2018070104.
Анотація:
This chapter describes how functional nucleic acids, such as aptamers, antisense oligonucleotides (ASOs), small interfering (si) RNAs, and ribozymes are considered by some researchers as valuable tools to develop therapeutic agents. They have not been particularly fast in reaching the market as medicines, due to endogenous barriers to extracellular trafficking and cellular uptake of nucleic acids and their inherent instability when applied in vivo. However, research carried out by the nucleic acid engineering community and pharmaceutical companies to circumvent these obstacles has led to the approval of a few aptamers and ASOs as drugs. Nucleic acid therapeutics are usually administered locally to diseased tissue. The drug candidates currently in clinical trials commonly use the same administration methods as previously licensed nucleic acid therapeutics. These administration techniques carry their own safety risks and advantages. In this article, the present state is discussed and prospective options for the use ASOs and aptamers as drugs are listed.
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Thakkar, H., A. N. Butt, J. Powrie, R. Holt, and R. Swaminathan. "Circulating Nucleic Acids in the Assessment of Endogenous Growth Hormone Production." Annals of the New York Academy of Sciences 1137, no. 1 (August 2008): 58–65. http://dx.doi.org/10.1196/annals.1448.003.
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Paramasivam, Prasath, Martin Stöter, Eloina Corradi, Irene Dalla Costa, Andreas Höijer, Stefano Bartesaghi, Alan Sabirsh, et al. "Quantitative intracellular retention of delivered RNAs through optimized cell fixation and immunostaining." RNA 28, no. 3 (December 23, 2021): 433–46. http://dx.doi.org/10.1261/rna.078895.121.
Анотація:
Detection of nucleic acids within subcellular compartments is key to understanding their function. Determining the intracellular distribution of nucleic acids requires quantitative retention and estimation of their association with different organelles by immunofluorescence microscopy. This is particularly important for the delivery of nucleic acid therapeutics, which depends on endocytic uptake and endosomal escape. However, the current protocols fail to preserve the majority of exogenously delivered nucleic acids in the cytoplasm. To solve this problem, by monitoring Cy5-labeled mRNA delivered to primary human adipocytes via lipid nanoparticles (LNP), we optimized cell fixation, permeabilization, and immunostaining of a number of organelle markers, achieving quantitative retention of mRNA and allowing visualization of levels that escape detection using conventional procedures. The optimized protocol proved effective on exogenously delivered siRNA, miRNA, as well as endogenous miRNA. Our protocol is compatible with RNA probes of single molecule fluorescence in situ hybridization (smFISH) and molecular beacon, thus demonstrating that it is broadly applicable to study a variety of nucleic acids in cultured cells.
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Basak, Ranjan, Naveen Kumar Nair, and Indraneel Mittra. "Evidence for cell-free nucleic acids as continuously arising endogenous DNA mutagens." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 793-794 (November 2016): 15–21. http://dx.doi.org/10.1016/j.mrfmmm.2016.10.002.
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Scholtissek, Benedikt, Sabine Zahn, Judith Maier, Sophie Klaeschen, Christine Braegelmann, Michael Hoelzel, Thomas Bieber, Winfried Barchet, and Joerg Wenzel. "Immunostimulatory Endogenous Nucleic Acids Drive the Lesional Inflammation in Cutaneous Lupus Erythematosus." Journal of Investigative Dermatology 137, no. 7 (July 2017): 1484–92. http://dx.doi.org/10.1016/j.jid.2017.03.018.
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Mahajan, Akanksha, Lisa Hurley, Serena Tommasini-Ghelfi, Corey Dussold, Alexander Stegh, and Chad Mirkin. "IMMU-53. STING-ING GLIOBLASTOMA WITH SPHERICAL NUCLEIC ACIDS." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi104—vi105. http://dx.doi.org/10.1093/neuonc/noab196.412.
Анотація:
Abstract The Stimulator of Interferon Genes (STING) pathway represents a major innate immune sensing mechanism for tumor-derived DNA. Modified cyclic dinucleotides (CDNs) that mimic the endogenous STING ligand cGAMP are currently being explored in patients with solid tumors that are amenable to intratumoral delivery. Inadequate bioavailability and insufficient lipophilicity are limiting factors for clinical CDN development, in particular when consideration is given to systemic administration approaches. We have shown that the formulation of oligonucleotides into Spherical Nucleic Acid (SNA) nanostructures, i.e.,the presentation of oligonucleotides at high density on the surface of nanoparticle cores, lead to biochemical and biological properties that are radically different from those of linear oligonucleotides. First-generation brain-penetrant siRNA-based SNAs (NCT03020017, recurrent GBM) have recently completed early clinical trials. Here, we report the development of a STING-agonistic immunotherapy by targeting cGAS, the sensor of cytosolic dsDNA upstream of STING, with SNAs presenting dsDNA at high surface density. The strategy of using SNAs exploits the ability of cGAS to raise STING responses by delivering dsDNA and inducing the catalytic production of endogenous CDNs. SNA nanostructures carrying a 45bp IFN-simulating dsDNA oligonucleotide, the most commonly used and widely characterized cGAS activator, potently activated the cGAS-STING pathway in vitro and in vivo. In a poorly immunogenic and highly aggressive syngeneic mouse glioma model, in which tumours were well-established, only one dose of intranasal treatment with STING-SNAs decelerated tumour growth, improved survival and importantly, was well-tolerated. Our use of SNAs addresses the challenges of nucleic acid delivery to intracranial tumor sites via intranasal route, exploits the binding of dsDNA molecules on the SNA surface to enhance the formation of a dimeric cGAS:DNA complex and establishes cGAS-agonistic SNAs as a novel class of immune-stimulatory modalities for triggering innate immune responses against tumor.
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Victoria, Joseph G., Chunlin Wang, Morris S. Jones, Crystal Jaing, Kevin McLoughlin, Shea Gardner, and Eric L. Delwart. "Viral Nucleic Acids in Live-Attenuated Vaccines: Detection of Minority Variants and an Adventitious Virus." Journal of Virology 84, no. 12 (April 7, 2010): 6033–40. http://dx.doi.org/10.1128/jvi.02690-09.
Анотація:
ABSTRACT Metagenomics and a panmicrobial microarray were used to examine eight live-attenuated viral vaccines. Viral nucleic acids in trivalent oral poliovirus (OPV), rubella, measles, yellow fever, varicella-zoster, multivalent measles/mumps/rubella, and two rotavirus live vaccines were partially purified, randomly amplified, and pyrosequenced. Over half a million sequence reads were generated covering from 20 to 99% of the attenuated viral genomes at depths reaching up to 8,000 reads per nucleotides. Mutations and minority variants, relative to vaccine strains, not known to affect attenuation were detected in OPV, mumps virus, and varicella-zoster virus. The anticipated detection of endogenous retroviral sequences from the producer avian and primate cells was confirmed. Avian leukosis virus (ALV), previously shown to be noninfectious for humans, was present as RNA in viral particles, while simian retrovirus (SRV) was present as genetically defective DNA. Rotarix, an orally administered rotavirus vaccine, contained porcine circovirus-1 (PCV1), a highly prevalent nonpathogenic pig virus, which has not been shown to be infectious in humans. Hybridization of vaccine nucleic acids to a panmicrobial microarray confirmed the presence of endogenous retroviral and PCV1 nucleic acids. Deep sequencing and microarrays can therefore detect attenuated virus sequence changes, minority variants, and adventitious viruses and help maintain the current safety record of live-attenuated viral vaccines.
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Burrill, Julia, Rachel Hotta, Barbara Daniel, and Nunzianda Frascione. "Accumulation of endogenous and exogenous nucleic acids in “Touch DNA” components on hands." ELECTROPHORESIS 42, no. 16 (June 10, 2021): 1594–604. http://dx.doi.org/10.1002/elps.202000371.
Дисертації з теми "Endogenous nucleic acids":
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Schattgen, Stefan A. "Sensing of Endogenous Nucleic Acids by the Innate Immune System during Viral Infection: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/764.
Анотація:
Innate sensing of nucleic acids lies at the heart of antiviral host defense. However, aberrant activation of innate sensors by host nucleic acids can also lead to the development of autoimmune diseases. Such host nucleic acids can also be released from stressed, damaged or dying cells into the tissue microenvironment. It however remains unclear how the extracellular nucleic acids impacts the quality of the host immune responses against viral infections. Using a mouse model of influenza A virus (IAV) infection, we uncovered an important immune-regulatory pathway that tempers the intensity of the host-response to infection. We found that host-derived DNA from necrotic cells accumulates in the lung microenvironment during IAV infection, and is sensed by the DNA receptor Absent in Melanoma 2 (AIM2). AIM2-deficiency resulted in severe immune pathology highlighted by enhanced recruitments of immune cells, and excessive systemic inflammation after IAV challenge, which led to increased morbidity and lethality in IAV-infected mice. Interestingly, these effects of AIM2 were largely independent of its ability to mediate IL-1β maturation through inflammasome complexes. Finally, ablation of accumulated DNA in the lung by transgenic expression of DNaseI in vivo had similar effects. Collectively, our results identify a novel mechanism of cross talk between PRR pathways, where sensing of hostderived nucleic acids limits immune mediated damage to virus infected tissues.
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Schattgen, Stefan A. "Sensing of Endogenous Nucleic Acids by the Innate Immune System during Viral Infection: A Dissertation." eScholarship@UMMS, 2003. http://escholarship.umassmed.edu/gsbs_diss/764.
Анотація:
Innate sensing of nucleic acids lies at the heart of antiviral host defense. However, aberrant activation of innate sensors by host nucleic acids can also lead to the development of autoimmune diseases. Such host nucleic acids can also be released from stressed, damaged or dying cells into the tissue microenvironment. It however remains unclear how the extracellular nucleic acids impacts the quality of the host immune responses against viral infections. Using a mouse model of influenza A virus (IAV) infection, we uncovered an important immune-regulatory pathway that tempers the intensity of the host-response to infection. We found that host-derived DNA from necrotic cells accumulates in the lung microenvironment during IAV infection, and is sensed by the DNA receptor Absent in Melanoma 2 (AIM2). AIM2-deficiency resulted in severe immune pathology highlighted by enhanced recruitments of immune cells, and excessive systemic inflammation after IAV challenge, which led to increased morbidity and lethality in IAV-infected mice. Interestingly, these effects of AIM2 were largely independent of its ability to mediate IL-1β maturation through inflammasome complexes. Finally, ablation of accumulated DNA in the lung by transgenic expression of DNaseI in vivo had similar effects. Collectively, our results identify a novel mechanism of cross talk between PRR pathways, where sensing of hostderived nucleic acids limits immune mediated damage to virus infected tissues.
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Ghildiyal, Megha. "Endogenous Small RNAs in the Drosophila Soma: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/459.
Анотація:
Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNAs have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, modes of target regulation and in the biological pathways they regulate.
Historically, siRNAs were believed to arise only from exogenous double-stranded RNA triggers in organisms lacking RNA-dependent RNA polymerases. However, the discovery of endogenous siRNAs in flies expanded the biological significance of siRNAs beyond viral defense. By high throughput sequencing we identified Drosophila endosiRNAs as 21 nt small RNAs, bearing a 2´-O-methyl group at their 3´ ends, and depleted in dicer-2 mutants.
Methylation of small RNAs at the 3´ end in the soma, is a consequence of assembly into a mature Argonaute2-RNA induced silencing complex. In addition to endo-siRNAs, we observed certain miRNAs or their miRNA* partners loading into Argonaute2. We discovered, that irrespective of its biogenesis, a miRNA duplex can load into either Argonaute (Ago1 or Ago2), contingent on its structural and sequence features, followed by assignment of one of the strands in the duplex as the functional or guide strand. Usually the miRNA strand is selected as the guide in complex with Ago1 and miRNA* strand with Ago2.
In our efforts towards finding 3´ modified small RNAs in the fly soma, we also discovered 24-28nt small RNAs in certain fly genotypes, particularly ago2 and dcr-2mutants. 24-28nt small RNAs share many features with piRNAs present in the germline, and a significant fraction of the 24-28nt small RNAs originate from similar transposon clusters as somatic endo-siRNAs. Therefore the same RNA can potentially act as a precursor for both endo-siRNA and piRNA-like small RNA biogenesis. We are analyzing the genomic regions that spawn somatic small RNAs in order to understand the triggers for their production. Ultimately, we want to attain insight into the underlying complexity that interconnects these small RNA pathways.
Dysregulation of small RNAs leads to defects in germline development, organogenesis, cell growth and differentiation. This thesis research provides vital insight into the network of interactions that fine-tune the small RNA pathways. Understanding the flow of information between the small RNA pathways, a great deal of which has been revealed only in the recent years, will help us comprehend how the pathways compete and collaborate with each other, enabling each other’s optimum function.
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Vasale, Jessica J. "Roles of Cellular RNA-Dependent RNA Polymerases in Endogenous Small RNA Pathways in Caenorhabditis elegans: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/481.
Анотація:
The RNA interference (RNAi) pathway in Caenorhabditis elegans is a two-step, small RNA-mediated silencing pathway. Unlike in other organisms, Dicer processing of double-stranded RNA into small interfering (si) RNAs is not sufficient in worms to induce gene silencing. The activity of cellular RNA-dependent RNA polymerase (RdRP) is necessary to synthesize a secondary pool of siRNAs, which interact with a unique class of Argonaute proteins to form the functional effector complexes that mediate silencing. The aims of this thesis were to: 1) characterize the role of RdRP family members in endogenous small RNA biogenesis; 2) identify the Argonaute proteins that interact with RdRP-dependent small RNAs; and 3) investigate the biological function of RdRP-dependent small RNA pathways in C. elegans.
In this thesis, I describe genetic, deep sequencing, and molecular studies, which identify 22G-RNAs as the most abundant class of endogenous small RNA in C. elegans. The 22G-RNAs resemble RdRP-dependent secondary siRNAs produced during exogenous RNAi, in that they possess a triphosphorylated 5’ guanine residue and exhibit a remarkable strand bias at target loci. Indeed, I show that 22G-RNAs are dependent on the activity of the RdRPs RRF-1 and EGO-1 and function in multiple distinct endogenous small RNA pathways. Interestingly, I have found that RRF-1 and EGO-1 function redundantly in the germline to generate 22G-RNAs that are dependent on and interact with members of an expanded family of worm-specific Argonaute (WAGO) proteins. The WAGO/22G-RNA pathway appears to be a transcriptome surveillance pathway that silences coding genes, pseudogenes, transposons, and non-annotated, or cryptic, transcripts. In contrast, I have found that EGO-1 alone is required for the biogenesis of a distinct class of 22G-RNAs that interact with the Argonaute CSR-1. Surprisingly, the CSR-1/22G-RNA pathway does not appear to silence its targets transcripts. Instead, the CSR-1/22G-RNA pathway is essential for the proper assembly of holocentric kinetochores and chromosome segregation.
Lastly, I show that a third endogenous small RNA pathway, the ERI pathway, is a two-step silencing pathway that requires the sequential activity of distinct RdRPs and Argonautes. In the first step of this pathway, the RdRP, RRF- 3, is required for the biogenesis of 26G-RNAs that associate with the Argonaute, ERGO-1. In the second step, RRF-1 and EGO-1 generate 22G-RNAs that associate with the WAGO Argonautes.
This work demonstrates how several C. elegans small RNAs pathways utilize RdRPs to generate abundant populations of small RNAs. These distinct categories of small RNAs function together with specific Argonaute proteins to affect gene expression, to play essential roles in development, and in the maintenance of genome and transcriptome integrity.
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Payet, Cloé. "Study of Interferon type I in Myasthenia Gravis." Thesis, Sorbonne université, 2021. http://www.theses.fr/2021SORUS517.
Анотація:
La Myasthénie Grave (MG) est une maladie due à des auto-anticorps contre le récepteur à l’acétylcholine (RACh). Le thymus est l’organe effecteur et est caractérisé par la surexpression d’interféron-β (IFN-β). Le but de ma thèse a été de comprendre l’implication des interférons de type I (IFN-I) dans la Myasthénie. Tout d’abord, j’ai démontré qu’aucune signature IFN-I n’est détectée dans le sérum ou les PBMC des patients. La signature IFN-I est donc bien spécifique du thymus et mon objectif a été de comprendre les causes de cette surexpression. L’induction des IFN-I est liée aux infections pathogènes mais dans certaines pathologies à des acides nucléiques endogènes (ANe). J’ai démontré que des molécules mimant des ANe induisent l’expression d’IFN-β et du RACh par les cellules épithéliales thymiques (CET) et dans le thymus de souris. J’ai émis l’hypothèse que ces ANe pouvaient provenir de thymocytes nécrotiques. J’ai donc induit la nécrose des thymocytes in vivo et in vitro et montré que cela induit la surexpression de l’IFN-β et du RACh dans les CET et dans le thymus de souris traitées à la dexaméthasone. Dans les thymus MG, j’ai aussi observé une diminution des macrophages, cellules nécessaires pour l’élimination des cellules apoptotiques. Chez la souris, une déplétion en macrophages augmente la nécrose des thymocytes et induit l’expression d’IFN-I et de RACh. Par conséquent, dans le thymus MG un défaut en macrophage pourrait empêcher l’élimination des thymocytes apoptotiques. Ces derniers passant en nécrose libéreraient alors des acides nucléiques activant les voies de la signalisation de l’immunité innée responsable de la signature IFN-β dans le thymus des patients MGMyasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the acetylcholine receptor (AChR). The thymus of patients is the effector organ and is characterized by chronic overexpression of interferon (IFN)-β. My PhD aimed to understand the implication of IFN-I in MG. First, I demonstrated that no IFN-I signature is detected in serum and PBMC of patients. IFN-I signature is specific to the thymus and I investigated the cause of this overexpression. IFN-I is produced in response to pathogen infection but also in response to endogenous nucleic acids (eNA) in diseases, such as interferonopathies. I demonstrated that molecules mimicking eNA, such as double-stranded DNA or RNA induced the overexpression of IFN-β and of AChR in human thymic epithelial cells (TEC) or in the thymus of mice. As I was suspecting eNA to be released by necrotic cells, I induced thymocyte necrosis in in vitro or in vivo models. I then showed an increased IFN-I signature and the expression of AChR in TEC and in the thymus of mice treated with dexamethasone. In addition, I observed in the MG thymus a decrease in thymic macrophages, cells responsible for the clearance of apoptotic cells. In mice, depletion of thymic macrophages led to an increase in necrotic thymocytes associated with IFN-I and AChR expression. Consequently, I hypothesize that in the MG thymus, a decrease in the number of macrophages may alter the processing of apoptotic cells leading to the release of eNA from necrotic thymocytes. These eNA would activate innate immunity signaling pathways leading to the IFN-β signature which would induce thymic changes self-sensitization against AChR
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Ta, Tuong Chi. "The essential fatty acid linoleic acid is the endogenous ligand for the Orphan nuclear receptor Hepatocyte nuclear factor 4 Aplha." Diss., UC access only, 2009. http://proquest.umi.com/pqdweb?did=1871881951&sid=1&Fmt=7&clientId=48051&RQT=309&VName=PQD.
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Halter, Bailey Anne. "Effects of exogenous and endogenous factors on appetite regulation in broiler chicks and Japanese quail." Thesis, Virginia Tech, 2021. http://hdl.handle.net/10919/103601.
Анотація:
Understanding how appetite is regulated, via exogenous or endogenous factors, is essential to animal agriculture in order to maximize production capabilities, as well as in human medicine to generate ways to treat conditions such as eating disorders or obesity. The aim of this thesis was to evaluate the effects of ferulic acid (FA), an exogenous factor found within plant cells, and oxyntomodulin (OXM), an endogenous hormone generated in the gastrointestinal tract, on food intake in avian models, as well as elucidate the hypothalamic mechanisms responsible. In broiler chicks (Gallus gallus), FA administered peripherally (IP) resulted in a transient yet potent reduction of food intake. A behavior analysis revealed that FA-treated chicks defecated fewer times than control birds. Within the arcuate nucleus (ARC) there was an increase in c-Fos immunoreactivity, indicating neuronal activation, in FA-treated chicks. Within the hypothalamus, there was a decrease in mRNA abundance of galanin, ghrelin, melanocortin receptor 3, and pro-opiomelanocortin (POMC), however within the ARC there was a decrease in POMC and an increase in c-Fos mRNA after FA treatment. OXM, a proglucagon-derived peptide produced in the gastrointestinal tract, administered intracerebroventricularly (ICV) or IP in Japanese quail (Coturnix japonica), resulted in a decrease in food intake for 3 hours post-injection. There was an increase in c-Fos immunoreactivity within the ARC as well as the dorsomedial nucleus (DMN) in quail ICV injected with OXM. In conclusion, these novel data provide insights on the similarities and differences between factors that can affect appetite regulation via anorexigenic effects.Master of Science
Exogenous and endogenous factors affect appetite regulation. Exogenous factors originate in feed components, additives, and other environmental factors that can affect bodily functions but are derived from an external source. Endogenous factors are made within the body, such as hormones and neurotransmitters, usually in response to a stimulus, and serve to communicate signals both locally and distantly in the body. Ferulic acid (FA), a natural exogenous factor originating within plant cells, is found in commonly consumed plant-based foods. When administered peripherally into broiler chicks (meat-type birds), FA caused a direct and potent, yet quickly diminishing, decrease in food intake via activation of cells within the hypothalamus, the region of the brain that is responsible for appetite regulation. Oxyntomodulin (OXM), an endogenous peptide hormone generated within the gastrointestinal tract in response to the digestion of nutrients, is known to decrease food intake in humans, rodents, and the broiler chick. However, its effects in Japanese quail, a model closer to a "wild-type" bird, are unknown. Quail injected peripherally (outside the brain) or intracerebroventricularly (ICV; into lateral ventricle of brain) with OXM showed a reduction in food intake that was more persistent than FA's effects with the effects also mediated via activation within the hypothalamus, although through slightly different molecular mechanisms. Understanding different factors that can regulate appetite in animals is necessary for agricultural applications to maximize production and improve health and welfare, as well as in humans to elucidate methods to treat appetite-related conditions, such as eating disorders and obesity.
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Eskandari, Roozbeh. "DEVELOPMENT OF NOVEL SYNTHETIC ROUTES TO THE EPOXYKETOOCTADECANOIC ACIDS (EKODES) AND THEIR BIOLOGICAL EVALUATION AS ACTIVATORS OF THE PPAR FAMILY OF NUCLEAR RECEPTORS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1441365802.
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Ellis, Matthew. "An Investigation Into the Fate of a C5'-Uridinyl Radical." University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513355069432417.
Частини книг з теми "Endogenous nucleic acids":
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Tsukahara, Ryoko, Tamotsu Tsukahara, and Gabor Tigyi. "Regulation of the Nuclear Hormone Receptor Pparγ by Endogenous Lysophosphatidic Acids (LPAS)." In Lysophospholipid Receptors, 349–72. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2013. http://dx.doi.org/10.1002/9781118531426.ch16.
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Sharma, Sahil, and Cynthia M. Sharma. "Identification of RNA Binding Partners of CRISPR-Cas Proteins in Prokaryotes Using RIP-Seq." In Methods in Molecular Biology, 111–33. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1851-6_6.
Анотація:
AbstractCRISPR-Cas systems consist of a complex ribonucleoprotein (RNP) machinery encoded in prokaryotic genomes to confer adaptive immunity against foreign mobile genetic elements. Of these, especially the class 2, Type II CRISPR-Cas9 RNA-guided systems with single protein effector modules have recently received much attention for their application as programmable DNA scissors that can be used for genome editing in eukaryotes. While many studies have concentrated their efforts on improving RNA-mediated DNA targeting with these Type II systems, little is known about the factors that modulate processing or binding of the CRISPR RNA (crRNA) guides and the trans-activating tracrRNA to the nuclease protein Cas9, and whether Cas9 can also potentially interact with other endogenous RNAs encoded within the host genome. Here, we describe RIP-seq as a method to globally identify the direct RNA binding partners of CRISPR-Cas RNPs using the Cas9 nuclease as an example. RIP-seq combines co-immunoprecipitation (coIP) of an epitope-tagged Cas9 followed by isolation and deep sequencing analysis of its co-purified bound RNAs. This method can not only be used to study interactions of Cas9 with its known interaction partners, crRNAs and tracrRNA in native systems, but also to reveal potential additional RNA substrates of Cas9. For example, in RIP-seq analysis of Cas9 from the foodborne pathogen Campylobacter jejuni (CjeCas9), we recently identified several endogenous RNAs bound to CjeCas9 RNP in a crRNA-dependent manner, leading to the discovery of PAM-independent RNA cleavage activity of CjeCas9 as well as non-canonical crRNAs. RIP-seq can be easily adapted to any other effector RNP of choice from other CRISPR-Cas systems, allowing for the identification of target RNAs. Deciphering novel RNA-protein interactions for CRISPR-Cas proteins within host bacterial genomes will lead to a better understanding of the molecular mechanisms and functions of these systems and enable us to use the in vivo identified interaction rules as design principles for nucleic acid-targeting applications, fitted to each nuclease of interest.
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Shi, Congjian, Hongqin Yang, Zhengchao Wang, and Zhenghong Zhang. "Regulation of Exosomes in the Pathogenesis of Breast Cancer." In Global Women's Health [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.95858.
Анотація:
Extracellular vesicles (EVs) are a heterogeneous group of endogenous nanoscale vesicles that are secreted by various cell types. Based on their biogenesis and size distribution, EVs can be broadly classified as exosomes and microvesicles. Exosomes are enveloped by lipid bilayers with a size of 30–150 nm in diameter, which contain diverse biomolecules, including lipids, proteins and nucleic acids. Exosomes transport their bioactive cargoes from original cells to recipient cells, thus play crucial roles in mediating intercellular communication. Breast cancer is the most common malignancy among women and remains a major health problem worldwide, diagnostic strategies and therapies aimed at breast cancer are still limited. Growing evidence shows that exosomes are involved in the pathogenesis of breast cancer, including tumorigenesis, invasion and metastasis. Here, we provide a straightforward overview of exosomes and highlight the role of exosomes in the pathogenesis of breast cancer, moreover, we discuss the potential application of exosomes as biomarkers and therapeutic tools in breast cancer diagnostics and therapeutics.
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Yang, Wen K., L. Y. Ch'ang, C. K. Koh, F. E. Myer, and M. D. Yang. "Mouse Endogenous Retroviral Long-Terminal-Repeat (LTR) Elements and Environmental Carcinoaenesis." In Progress in Nucleic Acid Research and Molecular Biology, 247–66. Elsevier, 1989. http://dx.doi.org/10.1016/s0079-6603(08)60175-0.
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Shivshankar M., Gunjegaonkar, Joshi Amol A., Wankhede Sagar B., Siraskar Balasaheb D., Merekar Abhijit N., and Shinde Sachin D. "Potential Defensive Involvement of Methyl Jasmonate in Oxidative Stress and Its Related Molecular Mechanisms." In Plant Hormones - Recent Advances, New Perspectives and Applications [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.102783.
Анотація:
Jasmonic acid (JA), cytokinins (CK), gibberellins (GA), abscisic acid (ABA), ethylene (ET), and salicylic acid (SA) are potent plant stress hormones (phytohormones/PTH). Methyl jasmonate (MeJA), a volatile ester of JA, is derived from the petals of Jasminum grandiflorum (jasmine). The MeJA has been meticulously confirmed for its food, agricultural, and therapeutic uses in the treatment of a range of serious illnesses. Several scientific articles have studied and reported on the role of free radicals in the development of life-threatening clinical illnesses. The inflammatory signaling pathway is triggered by a weak or interfering endogenous antioxidant system, or the elaborated production of free radicals, which causes damage to key cellular components. The current chapter focused on and demonstrated MeJA’s multifunctional role in antioxidant and anti-inflammatory signaling mechanisms such as inhibition of NF-B (nuclear factor kappa-light-chain-enhancer of activated B cells), mitogen-activated protein kinase (MAPK or MAP kinase) pathway inhibition/down-regulation of pro-inflammatory mediators (IL, TNF-), cyclo-oxygenase (COX), and (LOX). The antioxidant effect of MeJA’s interaction with miRNA, transcription of nuclear factor erythroid 2-related 2 (Nfr2), activation of sirtuins (SIRTs), antioxidant and redox signaling pathway were also discussed in the chapter.
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Onyike, Chiadi U. "Stimulants and Dopamine Augmenters." In Psychiatric Aspects of Neurologic Diseases. Oxford University Press, 2008. http://dx.doi.org/10.1093/oso/9780195309430.003.0024.
Анотація:
Stimulants are typically prescribed for their positive effects on mood, motivation, alertness, arousal, and energy. They are believed to exert their pharmacologic effects by increasing synaptic release of endogenous catecholamines (norepinephrine and dopamine) while simultaneously blocking catecholamine reuptake at the nerve terminals. Themost commonly used ‘‘traditional’’ agents are methylphenidate and dextroamphetamine. Methylphenidate reaches peak blood levels in 1 to 3 hours and has an elimination half-life of 2 to 3 hours. Dextroamphetamine reaches peak levels in 2 to 4 hours and has an elimination half-life of 3 to 6 hours. Controlled-release formulations are available, allowing for dosing once daily. Dextroamphetamine is excreted primarily in the urine in unchanged form, whereas methylphenidate is excreted mainly as ritalinic acid. The newer generation stimulant modafinil has been marketed in the United States since 1998. Initially used in the treatment of narcolepsy, it is now prescribed for a wider range of conditions because of its positive effects on wakefulness, vigilance, cognitive performance, and mood. Its pharmacologic effects are thought to result primarily from the stimulation of wakefulness-promoting orexinergic neurons in the anterior hypothalamus. Inhibition of norepinephrine reuptake in the ventrolateral preoptic nucleus and of dopamine reuptake (by binding to the transporter) may contribute to its action. Modafinil is administered orally, achieves peak plasma concentrations in 2 to 4 hours, and has an elimination half-life of 12 to 15 hours. It is 90% metabolized in the liver, and its metabolites are excreted in the urine. The ergot alkaloids bromocriptine and pergolide are familiar to most neurologists in their use in the treatment of Parkinson’s disease (PD) and migraine headache. These dopamine receptor agonists are also used in neuropsychiatry in the treatment of apathetic states in patients recovering from brain trauma, cerebral anoxia, and strokes. Amantadine is another familiar agent used in the treatment of PD and drug-induced parkinsonism. In addition to other effects in the central nervous system (CNS), amantadine facilitates dopamine release and inhibits its reuptake. It thus has modest ‘‘stimulant-like’’ effects useful in the treatment of executive dysfunction syndromes, particularly in patients with dementia. Bupropion is a dopamine and norepinephrine reuptake inhibitor. It usually is prescribed as a ‘‘nonsedating’’ antidepressant, but its potentiation of catecholamine neurotransmission results in modest stimulant-like clinical effects.
Тези доповідей конференцій з теми "Endogenous nucleic acids":
1
Sommer, Abigail, and Yael Vodovotz. "Chemical and Physical Stability of EPA and DHA Fortified Plant Milk Analogs." In 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/iwsn7066.
Анотація:
Fish oil and its component fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have demonstrated health benefits including reducing cardiac death risk and lowering inflammation. Yet, fish consumption is below recommended levels, indicating a need for accessible and safe sources of EPA and DHA. The objective of this study was to incorporate EPA- and DHA-rich oils from various sources into plant milks. It was hypothesized that physical and oxidative stability of fortified plant milks would differ by beverage and oil type due to varying structures, viscosity, and endogenous antioxidant compounds. Four beverage types (water, oat milk, soymilk, and almond milk) and three oil types (high-oleic sunflower oil, fish oil, and yeast oil plus algae oil) were utilized. The physical and chemical properties of the beverages were monitored over 15 days at 4°C and 55°C. Turbidity, viscosity, and color were analyzed. The oil droplet size was measured using dynamic light scattering. Oxidation was measured using peroxide value, thiobarbituric acid reactive substances, and low-field nuclear magnetic resonance. Turbidity did not differ between samples. Viscosity was influenced by beverage type (water, 0.5 mPa⋅s; soy, 9 mPa⋅s; oat, 39 mPa⋅s, almond, 48 mPa⋅s) but not oil type. Color was affected by beverage and oil type. Beverage but not oil type influenced mean particle size (D32) (soy, 533nm; water, 776nm; oat, 1190nm; almond, 1688nm). Beverages with no oil or sunflower oil had approximately 50% lower levels of oxidation as compared to those with fish oil and yeast/algae oil. Soymilk samples with fish or yeast/algae oil oxidized approximately 25-140% less than other beverages. Future work will include sensory evaluation and a clinical study to assess bioavailability, safety, and compliance. The analysis of fortified plant milks will help determine the optimal source and vehicle for EPA and DHA, ultimately resulting in a commercially viable beverage.