Transcriptional control mechanisms chart the course of the inflammatory response by synthesizing mRNAs encoding proteins that promote or inhibit inflammation. Because these mRNAs can be long-lived, ...turning off their synthesis does not rapidly stop or change the direction of inflammation. Post-transcriptional mechanisms that modify mRNA stability and/or translation provide more rapid and flexible control of this process and are particularly important in coordinating the initiation and resolution of inflammation. Here, I review the surprising variety of post-transcriptional control mechanisms that regulate the initiation and resolution of inflammation and discuss how these mechanisms are integrated to coordinate this essential process.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The cytokine-encoding messenger RNA (mRNA) molecules transcribed in the nucleus acquire a protein coat that facilitates nuclear export, influences cytoplasmic localization, and determines stability ...and translational competence. The composition of this coat is determined by sequence elements that recruit proteins that influence the rate of translation and/or mRNA decay. Some of these regulatory proteins direct their associated mRNA molecules to discrete cytoplasmic foci (stress granules and processing bodies) that are essential in 'programming' mRNA 'metabolism'. Studies have begun to identify how these various mechanisms are integrated and regulated to determine the amount of cytokine production in cells involved in immune responses. Understanding of these mechanisms has identified targets for the development of new classes of immunomodulatory drugs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transfer RNA (tRNA) is traditionally considered to be an adaptor molecule that helps ribosomes to decode messenger RNA (mRNA) and synthesize protein. Recent studies have demonstrated that tRNAs also ...serve as a major source of small non-coding RNAs that possess distinct and varied functions. These tRNA fragments are heterogeneous in size, nucleotide composition, biogenesis and function. Here we describe multiple roles that tRNA fragments play in cell physiology and discuss their relevance to human health and disease.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Stress granules (SGs) are membrane-less ribonucleoprotein (RNP)-based cellular compartments that form in the cytoplasm of a cell upon exposure to various environmental stressors. SGs contain a large ...set of proteins, as well as mRNAs that have been stalled in translation as a result of stress-induced polysome disassembly. Despite the fact that SGs have been extensively studied for many years, their function is still not clear. They presumably help the cell to cope with the encountered stress, and facilitate the recovery process after stress removal upon which SGs disassemble. Aberrant formation of SGs and impaired SG disassembly majorly contribute to various pathological phenomena in cancer, viral infections, and neurodegeneration.
The assembly of SGs is largely driven by liquid-liquid phase separation (LLPS), however, the molecular mechanisms behind that are not fully understood. Recent studies have proposed a novel mechanism for SG formation that involves the interplay of a large interaction network of mRNAs and proteins. Here, we review this novel concept of SG assembly, and discuss the current insights into SG disassembly.
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•Multivalency is the main driver for LLPS leading to SG assembly.•Proteins essential for multivalency-driven LLPS are multidomain proteins.•PTMs play a role in regulating SG formation and disassembly.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We show that global de Sitter space is unstable to particle creation, even for a massive free field theory with no self-interactions. The O(4,1) de Sitter invariant state is a definite phase coherent ...superposition of particle and antiparticle solutions in both the asymptotic past and future and, therefore, is not a true vacuum state. In the closely related case of particle creation by a constant, uniform electric field, a time symmetric state analogous to the de Sitter invariant one is constructed, which is also not a stable vacuum state. We provide the general framework necessary to describe the particle creation process, the mean particle number, and dynamical quantities such as the energy-momentum tensor and current of the created particles in the de Sitter and electric field backgrounds respectively in real time, establishing the connection to kinetic theory. We compute the energy-momentum tensor for adiabatic vacuum states in de Sitter space initialized at early times in global S super(3) sections and show that particle creation in the contracting phase results in exponentially large energy densities at later times, necessitating an inclusion of their backreaction effects and leading to large deviation of the spacetime from global de Sitter space before the expanding phase can begin.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Exchange Ideologies documents the social world of Aleppo's traders before the destruction of the city, exploring changing conceptions of commerce in Syria. Syria's traders have been seen as embodying ...a timeless culture of the bazaar, or an ahistorical Islamic culture of trade. Other accounts portray them as venal figures, motivated only by profit, and commerce as a purely instrumental pursuit. Rejecting both approaches, Paul Anderson traces the diverse social structures, and notions of language, through which Aleppo's merchants understood and construed commerce and the figure of the merchant during a period of economic liberalization in the 2000s. Rather than seeing these social structures and representations as expressions of a timeless bazaar culture, or as shaped only by Islamic tradition, Exchange Ideologies relates them to processes of politically managed economic liberalization and the Syrian regime's attempts to ensure its own survival in the midst of change. In doing so, Anderson provides an account of economic liberalization in Syria as a social and cultural process as much as a political and economic one.
Phase transitions that alter the physical state of ribonucleoprotein particles contribute to the spacial and temporal organization of the densely packed intracellular environment. This allows cells ...to organize biologically coupled processes as well as respond to environmental stimuli. RNA plays a key role in phase separation events that modulate various aspects of RNA metabolism. Here, we review the role that RNA plays in ribonucleoprotein phase separations.
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•RNA can play an active (templating, structural) or passive role in phase separation.•Phase separations cause formation of membrane-less organelles (MLOs).•Biophysical properties of MLOs are driven by RNA–protein interactions.•Different MLOs incorporate different RNA species
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Total joint replacement is common and increasing. Many of these patients have low bone mineral density preoperatively, and arthroplasty leads to bone loss. As falls are common before and after ...arthroplasty, it is unsurprising that periprosthetic fractures, defined as those associated with an orthopedic device, whether a joint replacement or other internal fixation devices, are not rare. These fractures engender morbidity and mortality comparable to osteoporosis-related hip fractures but remain largely unrecognized and untreated by osteoporosis/metabolic bone disease clinicians. Indeed, recent osteoporosis guidelines are silent regarding periprosthetic fractures. The purposes of this clinical review are to briefly describe the epidemiology of arthroplasty procedures and periprosthetic fractures, raise awareness that these fractures are osteoporosis-related, and suggest approaches likely to reduce their occurrence. Notably, bone health evaluation is essential following the occurrence of a periprosthetic fracture to reduce subsequent fracture risk. Importantly, in addition to such secondary fracture prevention, primary prevention, i.e., bone health assessment and optimization prior to elective orthopedic procedures, is appropriate.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Adsorption desalination is a promising technology that has recently been investigated. Most of the reported adsorption desalination systems use silica gel as the adsorbent and despite the high ...stability, it suffers from limited water uptake capabilities leading to a low system performance. Metal-organic frameworks (MOFs) are porous materials with high surface area, pore size, tunable pore geometry and hence providing high adsorption capacity. Currently, limited MOF materials with high water adsorption capabilities and hydrothermal stability are commercially available. CPO-27(Ni) and aluminium fumarate are two commercially available MOFs that have a maximum water uptake of 0.47 gH2O·gads−1 and 0.53 gH2O·gad−1, respectively. Another MOF, MIL-101(Cr), exhibits superior water adsorption uptake of 1.47 gH2O·gad−1 but currently can only be produced in lab-scale.
The thermodynamic cycle performance of a two beds adsorption system was evaluated using Simulink software to assess the suitability of those MOFs for adsorption desalination and their performance under different operating conditions. The CPO-27(Ni) was found to produce around 4.3m3·(ton·day)−1 at an evaporation temperature of 5°C while aluminium fumarate produced around 6m3·(ton·day)−1 at an evaporation temperature of 20°C. As for MIL-101(Cr), the water production rate at 20°C was 11m3·(ton·day)−1 highlighting the potential of this material compared to other adsorbents.
•CPO-27(Ni), aluminium fumarate and MIL-101(Cr) were investigated for adsorption desalination application.•Optimum desorption temperature for CPO-27(Ni) was higher than 110°C and for aluminium fumarate was as low as 70°C.•CPO-27(Ni) outperformed other materials at low evaporation temperature (5°C) and high regeneration temperatures.•MIL-101(Cr) and aluminium fumarate outperformed CPO-27(Ni) and silica gel at high evaporation temperature (20°C).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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