639 research outputs found

    Divergent Modulation of Proteostasis in Prostate Cancer

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    Ballar, Petek/0000-0002-6189-1818WOS: 000530838600006PubMed: 32274755Proteostasis regulates key cellular processes such as cell proliferation, differentiation, transcription, and apoptosis. the mechanisms by which proteostasis is regulated are crucial and the deterioration of cellular proteostasis has been significantly associated with tumorigenesis since it specifically targets key oncoproteins and tumor suppressors. Prostate cancer (PCa) is the second most common cause of cancer death in men worldwide. Androgens mediate one of the most central signaling pathways in all stages of PCa via the androgen receptor (AR). in addition to their regulation by hormones, PCa cells are also known to be highly secretory and are particularly prone to ER stress as proper ER function is essential. Alterations in various complex signaling pathways and cellular processes including cell cycle control, transcription, DNA repair, apoptosis, cell adhesion, epithelial-mesenchymal transition (EMT), and angiogenesis are critical factors influencing PCa development through key molecular changes mainly by posttranslational modifications in PCa-related proteins, including AR, NKX3.1, PTEN, p53, cyclin D1, and p27. Several ubiquitin ligases like MDM2, Siah2, RNF6, CHIP, and substrate-binding adaptor SPOP; deubiquitinases such as USP7, USP10, USP26, and USP12 are just some of the modifiers involved in the regulation of these key proteins via ubiquitin-proteasome system (UPS). Some ubiquitin-like modifiers, especially SUMOs, have been also closely associated with PCa. on the other hand, the proteotoxicity resulting from misfolded proteins and failure of ER adaptive capacity induce unfolded protein response (UPR) that is an indispensable signaling mechanism for PCa development. Lastly, ER-associated degradation (ERAD) also plays a crucial role in prostate tumorigenesis. in this section, the relationship between prostate cancer and proteostasis will be discussed in terms of UPS, UPR, SUMOylation, ERAD, and autophagy.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [SBAG-108S056/114S062]; Ege University internal funds; BAGEP Award of the Science Academy; Pfizer-TurkeyPfizer; COST Action (PROTEOSTASIS)European Cooperation in Science and Technology (COST) [BM1307]; COST (European Cooperation in Science and Technology)European Cooperation in Science and Technology (COST)Work by PBK is supported by the Scientific and Technological Research Council of Turkey (TUBITAK, SBAG-108S056/114S062), Ege University internal funds, BAGEP Award of the Science Academy with funding supplied by Pfizer-Turkey, COST Action (PROTEOSTASIS BM1307), and by COST (European Cooperation in Science and Technology)

    Pharmacotherapy of Tinnitus

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    Tinnitus is a common symptom for which there is in most cases no causal therapy. The search for an improvement of tinnitus through pharmacological interventions has a long tradition. The observation that tinnitus can be transiently suppressed by the use of lidocaine has shown that the symptom is susceptible to pharmacotherapy. So far, however, no medication has been found for either acute or chronic subjective tinnitus that reliably leads to a long-term reduction or even complete disappearance of the symptom for the majority of tinnitus sufferers. Nevertheless, in everyday clinical life, drugs are frequently used, usually off-label, to relieve tinnitus or tinnitus-associated symptoms (e.g. sleep disturbance, depression, anxiety disorder or hearing loss). This chapter shows the different approaches to acute and chronic subjective tinnitus by means of pharmacotherapeutic interventions. Furthermore, this review reports on the scientific studies carried out in this area in recent years and explains the difficulties in finding a suitable medication for most forms of tinnitus. In addition, it reports on the pharmacotherapeutic options for objective tinnitus and describes the development of tinnitus as a side effect of certain drugs. Finally, possible target structures are mentioned, which should possibly be addressed in pharmacological studies in the near future

    Space missions for astronomy and astrophysics in Korea: past, present, and future

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    We review the history of space missions in Korea focusing on the field of astronomy and astrophysics. For each mission, scientific motivation and achievement are reviewed together with some technical details of the program, including mission schedule. This review includes ongoing and currently approved missions, as well as some planned ones. Within the admitted limitations of the authors' perspectives, some comments on the future direction of the space program for astronomy and astrophysics in Korea are made at the end of this review

    Failure of Percutaneous A1 pulley release in Trigger Digits

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    Mouse Models of Neural Tube Defects.

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    Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson's Disease

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    ª 2019 Elsevier Ltd. Current pharmacological treatments for Parkinson's disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD11Nsciescopu

    Bandgap engineering of two-dimensional semiconductor materials

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    © 2020 Springer Nature Limited Semiconductors are the basis of many vital technologies such as electronics, computing, communications, optoelectronics, and sensing. Modern semiconductor technology can trace its origins to the invention of the point contact transistor in 1947. This demonstration paved the way for the development of discrete and integrated semiconductor devices and circuits that has helped to build a modern society where semiconductors are ubiquitous components of everyday life. A key property that determines the semiconductor electrical and optical properties is the bandgap. Beyond graphene, recently discovered two-dimensional (2D) materials possess semiconducting bandgaps ranging from the terahertz and mid-infrared in bilayer graphene and black phosphorus, visible in transition metal dichalcogenides, to the ultraviolet in hexagonal boron nitride. In particular, these 2D materials were demonstrated to exhibit highly tunable bandgaps, achieved via the control of layers number, heterostructuring, strain engineering, chemical doping, alloying, intercalation, substrate engineering, as well as an external electric field. We provide a review of the basic physical principles of these various techniques on the engineering of quasi-particle and optical bandgaps, their bandgap tunability, potentials and limitations in practical realization in future 2D device technologies.11Nsciescopu

    Sensitization to cell death induced by soluble Fas ligand and agonistic antibodies with exogenous agents: A review

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    Modified oligonucleotides containing lithocholic acid in their backbones: Their enhanced cellular uptake and their mimicking of hairpin structures

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    Their enhanced cell permeability and their ability to mimic DNA structures make modified oligodeoxyribonucleotides (ODNs) very important substances for increasing our understanding of cell biology and for therapeutic applications. Lithocholic acid is a hydrophobic secondary bile acid that is a substrate of nuclear Pregnane X receptor (PXR). We designed and synthesized novel lithocholic acid-based ODNs (L-ODNs) by using a new phosphoramidite derived from lithocholic acid. By comparing data obtained from circular-dichroism, melting-point, and theoretical studies, we believe that these L-ODNs adopt DNA hairpin structures. Furthermore, L-ODNs have enhanced cellular uptake properties with respect to regular ODNs. To demonstrate their enhanced cell permeabilites, we carried out cellular uptake experiments of L-ODNs in HeLa cells. By attaching fluorescein as a fluorescence label and using confocal microscopy, we observed that the permeability of L-ODNs is much higher that that of natural ODNs.X1119sciescopu
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