Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and ...many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.
The amide bond represents a privileged motif in chemistry. The recent years have witnessed an explosion of interest in the development of new chemical transformations of amides. These developments ...cover an impressive range of catalytic N–C bond activation in electrophilic, Lewis acid, radical, and nucleophilic reaction pathways, among other transformations. Equally relevant are structural and theoretical studies that provide the basis for chemoselective manipulation of amidic resonance. This monograph on amide bonds offers a broad survey of recent advances in activation of amides and addresses various approaches in the field.
The 1957 Celebration of Poet Endre Ady as a Lieu de Mémoire In this dissertation, I examine the process of cult creation in the context of the nationwide celebrations of Hungarian poet Endre Ady ...organized in Romania in the 1950s. More broadly, I research how the post-war state-socialist power introduced its hero types in literature and theatre, thereby creating its own places of remembrance. Examining the ‘lieu de mémoire’ used in the sense rendered by Pierre Nora, it seems important that the new places of remembrance created by the power - museums, statues, heroes, oeuvres, literary evenings of theatres, etc. – create a sense of continuity, but in reality, they convey a radically new message, and try to achieve this mainly through a hero placed at the centre of the cult. In the retelling and activating of history (and the story), the disappearing difference between the ‘real’ and ‘would-be’ gives birth to a compulsion to repeat, which after a while leads to the emptying of the contents and the formation of double speech.
Biochar is a solid by-product of thermochemical conversion of biomass to bio-oil and syngas. It has a carbonaceous skeleton, a small amount of heteroatom functional groups, mineral matter, and water. ...Biochar’s unique physicochemical structures lead to many valuable properties of important technological applications, including its sorption capacity. Indeed, biochar’s wide range of applications include carbon sequestration, reduction in greenhouse gas emissions, waste management, renewable energy generation, soil amendment, and environmental remediation. Aside from these applications, new scientific insights and technological concepts have continued to emerge in the last decade. Consequently, a systematic update of current knowledge regarding the complex nature of biochar, the scientific and technological impacts, and operational costs of different activation strategies are highly desirable for transforming biochar applications into industrial scales. This communication presents a comprehensive review of physical activation/modification strategies and their effects on the physicochemical properties of biochar and its applications in environment-related fields. Physical activation applied to the activation of biochar is discussed under three different categories: I) gaseous modification by steam, carbon dioxide, air, or ozone; II) thermal modification by conventional heating and microwave irradiation; and III) recently developed modification methods using ultrasound waves, plasma, and electrochemical methods. The activation results are discussed in terms of different physicochemical properties of biochar, such as surface area; micropore, mesopore, and total pore volume; surface functionality; burn-off; ash content; organic compound content; polarity; and aromaticity index. Due to the rapid increase in the application of biochar as adsorbents, the synergistic and antagonistic effects of activation processes on the desired application are also covered.
COVID-19 is a highly heterogeneous and complex medical disorder; indeed, severe COVID-19 is probably amongst the most complex of medical conditions known to medical science. While enormous strides ...have been made in understanding the molecular pathways involved in patients infected with coronaviruses an overarching and comprehensive understanding of the pathogenesis of COVID-19 is lacking. Such an understanding is essential in the formulation of effective prophylactic and treatment strategies. Based on clinical, proteomic, and genomic studies as well as autopsy data severe COVID-19 disease can be considered to be the connection of three basic pathologic processes, namely a pulmonary macrophage activation syndrome with uncontrolled inflammation, a complement-mediated endothelialitis together with a procoagulant state with a thrombotic microangiopathy. In addition, platelet activation with the release of serotonin and the activation and degranulation of mast cells contributes to the hyper-inflammatory state. Auto-antibodies have been demonstrated in a large number of hospitalized patients which adds to the end-organ damage and pro-thrombotic state. This paper provides a clinical overview of the major pathogenetic mechanism leading to severe COVID-19 disease.
Sunlight-driven hydrogen production via photoreforming of aqueous solutions containing renewable compounds is an attractive option for sustainable energy generation with reduced carbon footprint. ...Nevertheless, the absence of photocatalysts combining high efficiency and stability upon solar light activation has up to date strongly hindered the development of this technology. Herein, two scarcely investigated iron(III) oxide polymorphs, beta- and epsilon -Fe sub(2)O sub(3), possessing a remarkable activity in sunlight-activated H sub(2) generation from aqueous solutions of renewable oxygenates (i.e., ethanol, glycerol, glucose) are reported. For beta-Fe sub(2)O sub(3) and epsilon -Fe sub(2)O sub(3), H sub(2) production rates up to 225 and 125 mmol h super(-1) m super(-2) are obtained, with significantly superior performances with respect to the commonly investigated alpha-Fe sub(2)O sub(3). Sunlight-activated photoreforming of renewable oxygenates promoted by Fe sub(2)O sub(3) nanosystems is a very attractive process for hydrogen production. In this context, scarcely investigated beta- and epsilon -Fe sub(2)O sub(3) polymorphs, fabricated by chemical vapor deposition, show very promising performances for photocatalytic solar hydrogen generation. The present approach holds a remarkable potential even for the synthesis of added-value by-products, paving the way to manifold technological applications.
Carbons with high surface area and large volume of ultramicropores were synthesized for CO sub(2) adsorption. First, mesoporous carbons were produced by soft-templating method using triblock ...copolymer Pluronic F127 as a structure directing agent and formaldehyde and either phloroglucinol or resorcinol as carbon precursors. The resulting carbons were mainly mesoporous with well-developed surface area, large total pore volume, and only moderate CO sub(2) uptake. To improve CO sub(2) adsorption, these carbons were subjected to KOH activation to enhance their microporosity. Activated carbons showed 2-3-fold increase in the specific surface area, resulting from substantial development of microporosity (3-5-fold increase in the micropore volume). KOH activation resulted in enhanced CO sub(2) adsorption at 760 mmHg pressure: 4.4 mmol g super(-1) at 25 degree C, and 7 mmol g super(-1) at 0 degree C. This substantial increase in the CO sub(2) uptake was achieved due to the development of ultramicroporosity, which was shown to be beneficial for CO sub(2) physisorption at low pressures. The resulting materials were investigated using low-temperature nitrogen physisorption, CO sub(2) sorption, and small-angle powder X-ray diffraction. High CO sub(2) uptake and good cyclability (without noticeable loss in CO sub(2) uptake after five runs) render ultramicroporous carbons as efficient CO sub(2) adsorbents at ambient conditions.
COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation ...syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.
New Insights into Modes of GPCR Activation Wang, Wenjing; Qiao, Yuhui; Li, Zijian
Trends in pharmacological sciences (Regular ed.),
April 2018, 2018-Apr, 2018-04-00, Letnik:
39, Številka:
4
Journal Article
Recenzirano
In classical G-protein-coupled receptor (GPCR) activation, GPCRs couple to a variety of heterotrimeric G proteins on the membrane and then activate downstream signaling pathways. More recently, GPCRs ...have been found to couple to different effector proteins, including different G protein subtypes and regulatory proteins, such as arrestins. Some novel modes of GPCR activation have been proposed to explain their complex behaviors. In this review, we summarize the main novel modes of GPCR activation, including biased activation, intracellular activation, dimerization activation, transactivation, and biphasic activation. In addition, we also discuss the relationship among the five modes to show the complex picture of GPCR activation. The complex activation modes regulate precisely GPCR downstream signaling, including physiological and pathological signaling. Thus, there is the potential to develop GPCR precision drugs that target precise GPCR activation modes to accurately strengthen their beneficial functions and block specific pathological processes.
GPCRs are the largest family of cell surface receptors and are significant drug targets.
In recent years, many advanced biochemical and biophysical methods, such as single molecule methods, and single particle electron cryomicroscopy, have been used to study GPCRs.
With advanced methods and in-depth research, several novel modes of GPCR activation have been discovered in addition to the classical activation (GPCR–G protein signaling pathways) mode. These diverse modes of GPCR activation help explain their complex behaviors.
Varied modes of GPCR activation allow the concept of precision drug development and provide a theoretical basis for the research and development of GPCR-targeted functionally selective drugs.
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