Abstract
Dnmt2, a member of the DNA methyltransferase superfamily, catalyzes the formation of 5-methylcytosine at position 38 in the anticodon loop of tRNAs. Dnmt2 regulates many cellular biological ...processes, especially the production of tRNA-derived fragments and intergenerational transmission of paternal metabolic disorders to offspring. Moreover, Dnmt2 is closely related to human cancers. The tRNA substrates of mammalian Dnmt2s are mainly detected using bisulfite sequencing; however, we lack supporting biochemical data concerning their substrate specificity or recognition mechanism. Here, we deciphered the tRNA substrates of human DNMT2 (hDNMT2) as tRNAAsp(GUC), tRNAGly(GCC) and tRNAVal(AAC). Intriguingly, for tRNAAsp(GUC) and tRNAGly(GCC), G34 is the discriminator element; whereas for tRNAVal(AAC), the inosine modification at position 34 (I34), which is formed by the ADAT2/3 complex, is the prerequisite for hDNMT2 recognition. We showed that the C32U33(G/I)34N35 (C/U)36A37C38 motif in the anticodon loop, U11:A24 in the D stem, and the correct size of the variable loop are required for Dnmt2 recognition of substrate tRNAs. Furthermore, mammalian Dnmt2s possess a conserved tRNA recognition mechanism.
In order to survive, bacteria continually sense, and respond to, environmental fluctuations. Stringent control represents a key bacterial stress response to nutrient starvation that leads to rapid ...and comprehensive reprogramming of metabolic and transcriptional patterns. In general, transcription of genes for growth and proliferation is downregulated, while those important for survival and virulence are upregulated. Amino acid starvation is sensed by depletion of the aminoacylated tRNA pools, and this results in accumulation of ribosomes stalled with non-aminoacylated (uncharged) tRNA in the ribosomal A site. RelA is recruited to stalled ribosomes and activated to synthesize a hyperphosphorylated guanosine analogue, (p)ppGpp, which acts as a pleiotropic secondary messenger. However, structural information about how RelA recognizes stalled ribosomes and discriminates against aminoacylated tRNAs is missing. Here we present the cryo-electron microscopy structure of RelA bound to the bacterial ribosome stalled with uncharged tRNA. The structure reveals that RelA utilizes a distinct binding site compared to the translational factors, with a multi-domain architecture that wraps around a highly distorted A-site tRNA. The TGS (ThrRS, GTPase and SpoT) domain of RelA binds the CCA tail to orient the free 3' hydroxyl group of the terminal adenosine towards a β-strand, such that an aminoacylated tRNA at this position would be sterically precluded. The structure supports a model in which association of RelA with the ribosome suppresses auto-inhibition to activate synthesis of (p)ppGpp and initiate the stringent response. Since stringent control is responsible for the survival of pathogenic bacteria under stress conditions, and contributes to chronic infections and antibiotic tolerance, RelA represents a good target for the development of novel antibacterial therapeutics.
Carbon dots (CDs) possess unique optical properties such as tunable photoluminescence (PL) and excitation dependent multicolor emission. The quenching and recovery of the fluorescence of CDs can be ...utilized for detecting analytes. The PL mechanisms of CDs have been discussed in previous articles, but the quenching mechanisms of CDs have not been summarized so far. Quenching mechanisms include static quenching, dynamic quenching, Förster resonance energy transfer (FRET), photoinduced electron transfer (PET), surface energy transfer (SET), Dexter energy transfer (DET) and inner filter effect (IFE). Following an introduction, the review (with 88 refs.) first summarizes the various kinds of quenching mechanisms of CDs (including static quenching, dynamic quenching, FRET, PET and IFE), the principles of these quenching mechanisms, and the methods of distinguishing these quenching mechanisms. This is followed by an overview on applications of the various quenching mechanisms in detection and imaging.
Graphical abstract
Schematic representation of the quenching mechanisms of carbon dots (CDs) which include static quenching, dynamic quenching, Förster resonance energy transfer (FRET), photoinduced electron transfer(PET), surface energy transfer (SET), Dexter energy transfer (DET) and inner filter effect (IFE). All these effects can be used to detect and image analytes.
The Ser/Leu-swapped genetic code can act as a genetic firewall, mitigating biohazard risks arising from horizontal gene transfer in genetically modified organisms. Our prior work demonstrated the ...orthogonality of this swapped code to the standard genetic code using a cell-free translation system comprised of 21 in vitro transcribed tRNAs. In this study, to advance this system for protein engineering, we introduce a natural/in vitro transcribed-hybrid tRNA set. This set combines natural tRNAs from Escherichia coli (excluding Ser, Leu, and Tyr) and in vitro transcribed tRNAs, encompassing anticodon-swapped tRNA
and tRNA
. This approach reduces the number of in vitro transcribed tRNAs required from 21 to only 4. In this optimized system, the production of a model protein, superfolder green fluorescent protein, increases to 3.5-fold. With this hybrid tRNA set, the Ser/Leu-swapped cell-free translation system will stand as a potent tool for protein production with reduced biohazard concerns in future biological endeavors.
Remittance inflows play a crucial role in Nepal's economy. Officially recorded remittances already amounted to almost a quarter of the Gross Domestic Product (GDP) in 2009. The 2008-09 global ...economic crises resulted in slower growth of remittance inflows in Nepal, leading directly to lower disposable income. This is a telling reminder of the importance of promoting a supportive environment for remittances. Nepali migration continues to increase as workers seek greater economic opportunities abroad. In this quest, Qatar is one of the important migration destinations for Nepali migrant workers. This report analyzes the migration and remittance transfer processes in the Qatar-Nepal Corridor in order to provide policy recommendations that would help improve the scale and impact of remittance transfers from Qatar to Nepal, and enhance the efficiency and integrity of migration and remittances in the corridor. The report identifies challenges in the migration process from Nepal to Qatar (related to high migration costs and their financing) and constraints in the remittance transfer process from Qatar to Nepal, which together limit the development and poverty reduction impact of remittance flows to Nepali households. As this report highlights, the Qatar-Nepal remittance corridor has several distinctive features. First, the majority of remittance flows from Qatar to Nepal are being transferred through officially regulated remittance channels. One of the reasons for this is actually the second feature of this corridor, namely, the officially managed migration process from Nepal to Qatar (as a result of which the majority of migrants are documented workers). The third feature is the contrast between the high competition and low prices of remittance services in this corridor on the one hand, and the contradictory rules and high costs incurred during the migration process on the other hand. Finally, as a by-product of the complex migration process which involves multiple players, financial transfers through informal mechanisms take place from Nepal to Qatar in order to pay the commissions of manpower agencies and middlemen.
Transfer of technologies (TT) takes place among various kinds of players, takes on various kinds of modalities and is done for various motivations. Its literature is very disjoint and disparate. It ...transcends several academic disciplines and professions. This paper presents a taxonomy defining the field in its entirety and delineating all of its facets in a manner that is parsimonious yet discriminating. Many potential uses for the taxonomy are identified. These include more effective teaching of TT subject matter.
•A combined micropolar and nanofluid effects of thermal system has been investigated.•Energy conversion is application for thermal system.•Thermal energy enhancement are observed with various values ...of pertinent parameters.•The results are comparison with other studies have been examined.
An applied thermal system for heat and mass transfer and energy management problem of hydromagnetic flow with magnetic and viscous dissipation effects micropolar nanofluids towards a stretching sheet has been studied. A system of partial differential equations for micropolar and nanofluid has been analyzed by a combination of the similarity transformation and accurate finite-difference method. Those solutions are used to obtain distributions of the local convective heat transfer coefficient and the stretching sheet temperature. The related importance dimensionless parameters are Prandtl number Pr, magnetic parameter M, material parameter K, Eckert number Ec, Brownian motion number Nb, thermophoresis parameter Nt and the Schmidt number Sc, respectively. The numerical results are indicated that an increasing in the magnetic parameter is given a decreasing in the values of the velocities and Nusselt number, or an increasing in the values of the shear stress, couple stress at the surface, temperature and concentration. The material parameter K has the opposite effect of magnetic field parameter on the values of the velocities, temperature, concentration, shear stress, Nusselt number and Schmidt number. The temperature is decreased as the Prandtl number increasing, or is increased as the Eckert number increasing. The concentration is decreased as Schmidt number increasing. At last, the study has been presented one multimedia video to show its main contain, it will be appeared at Elsevier AudioSlides website.
Growing Public Lindert, Peter H.
01/2004, Letnik:
1
eBook
Growing Public examines the question of whether social policies that redistribute income impose constraints on economic growth. Taxes and transfers have been debated for centuries, but only now can ...we get a clear view of the whole evolution of social spending. What kept prospering nations from using taxes for social programs until the end of the nineteenth century? Why did taxes and spending then grow so much, and what are the prospects for social spending in this century? Why did North America become a leader in public education in some ways and not others? Lindert finds answers in the economic history and logic of political voice, population aging, and income growth. Contrary to traditional beliefs, the net national costs of government social programs are virtually zero. This book not only shows that no Darwinian mechanism has punished the welfare states, but uses history to explain why this surprising result makes sense. Contrary to the intuition of many economists and the ideology of many politicians, social spending has contributed to, rather than inhibited, economic growth.
The rapid spread of large-scale and innovative social transfers in the developing world has made a key contribution to the significant reduction in global poverty over the last decade. Explaining how ...flagship anti-poverty programmes emerged, this book provides the first comprehensive account of the global growth of social assistance transfers in developing countries. Armando Barrientos begins by focusing on the ethical and conceptual foundations of social assistance, and he discusses the justifications for assisting those in poverty. He provides a primer on poverty analysis, and introduces readers to the theory of optimal transfers. He then shifts the focus to practice, and introduces a classification of social assistance programmes to help readers understand the diversity in approaches and design in developing countries. The book concludes with an analysis of the financing and politics of the emerging institutions and of their potential to address global poverty.
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