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Voters often rely on informational shortcuts, such as the background traits of politicians, to decide which candidates to support at the ballot box. One such background trait is family composition, particularly parental status. Research, however, has mostly overlooked whether the value-laden choices that politicians make regarding their families—like what neighborhoods they live in, where they worship, and what schools they send their children to—affect how constituents view them. We conduct a survey experiment in the U.S. that presents respondents with hypothetical biographies of politicians that randomly vary one of the most important decisions that politicians make regarding their families: whether to send them to public or private school. We find that: (1) voters are more inclined to vote for politicians with children in public school; and (2) this preference may be due to voters perceiving these politicians as both warmer and more committed to public services.

The objective of this study is to investigate the relationship between ease of doing business score (EDBS) and cost of business start-up procedures (CBS), age dependency ratio (ADR), strength of legal rights index (SLRI), time required to get electricity (TRGE), domestic credit to private sector (DCPS), and start-up procedures to register a business (SPRB). Since 2004, the World Bank evaluates 190 economies based on business regulatory indicators ignoring other factors that may be related to business environment. This paper investigates new factors related to EDBS ignored by the World Bank since 2004. The results of correlation analysis show a negative and significant correlation between EDB and CBS, ADR, TRGE, and SPRB. Nevertheless, a positive and significant correlation was found between EDB and SLRI and DCPS. The linear regression model finds that SLRI and DGPS affected EDB positively and significantly. However, TRGE and SPRB affected negatively to EDB. Asian policymakers should reinforce SLRI and increase DCPS. However, they should also reduce TRGE and SPRB to improve EDB. Further research should be conducted on other regions and test also other factors.

The Diachronic Corpus of Political Speeches (DCPS) is a collection of 1,500 full-length political speeches in English. It includes speeches delivered in countries where English is an official language (the US, Britain, Canada, Ireland) by English-speaking politicians in various settings from 1800 up to the present time. Enriched with semi-automatic morphosyntactic annotations and with discourse-pragmatic manual annotations, the DCPS is designed to achieve maximum representativeness and balance for political English speeches from major national English varieties in time, preserve detailed metadata, and enable corpus-based studies of syntactic, semantic and discourse-pragmatic variation and change on political corpora. For speeches given from 1950 onwards, video-recordings of the original delivery are often retrievable online. This opens up avenues of research in multimodal linguistics, in which studies on the integration of speech and gesture in the construction of meaning can include analyses of recurrent gestures and of multimodal constructions. This article discusses the issues at stake in preparing the video-recorded component of the DCPS for linguistic multimodal analysis, namely the exploitability of recordings, the segmentation and alignment of transcriptions, the annotation of gesture forms and functions in the software ELAN and the quantity of available gesture data.

International audience; Purpose of review: Evidence for adverse respiratory effects of occupational exposure to disinfectants and cleaning products (DCPs) has grown in the last two decades. The relationship between DCPs and asthma is well-documented, but questions remain regarding specific causal agents. Beyond asthma, associations between DCPs and COPD or chronic rhinitis are plausible and have been examined recently. The purpose of this review is to summarize recent advances on the effect of occupational exposure to DCP and chronic airway diseases. Recent findings: Recent epidemiological studies have often focused on healthcare workers and are characterized by efforts to improve assessment of exposure to specific DCPs. Despite increasing knowledge on the effect of DCPs on asthma, the burden of work-related asthma caused by DCPs has not decreased in the past decade, emphasizing the need to strengthen prevention efforts. Novel data suggest an association between occupational exposure to DCPs and other chronic airway diseases, such as rhinitis, COPD and poor lung function. Summary: Epidemiological and experimental data showed that many chemicals contained in DCPs are likely to cause airway damages, indicating that prevention strategies should target multiple products. Further research is needed to evaluate the impact of DCPs exposure on occupational airway diseases beyond asthma.

Significance In eukoryotes, 3′ to 5′ mRNA degradation is a major pathway to reduce mRNA levels and, thus, an important means to regulate gene expression. Herein, messenger RNA (mRNA) is hydrolyzed from the 3′ end by the exosome complex, producing short capped RNA fragments, which are decapped by DcpS. Our data show that DcpS is only active on mRNA that have undergone prior processing by the exosome. This DcpS selection mechanism is conserved from yeast to humans and is caused by the inability of the enzyme to undergo structural changes that are required for the formation of a catalytically active state around long mRNA transcripts. Our work thus reveals the mechanistic basis that ensures an efficient interplay between DcpS and the exosome., The 5′ messenger RNA (mRNA) cap structure enhances translation and protects the transcript against exonucleolytic degradation. During mRNA turnover, this cap is removed from the mRNA. This decapping step is catalyzed by the Scavenger Decapping Enzyme (DcpS), in case the mRNA has been exonucleolyticly shortened from the 3′ end by the exosome complex. Here, we show that DcpS only processes mRNA fragments that are shorter than three nucleotides in length. Based on a combination of methyl transverse relaxation optimized (TROSY) NMR spectroscopy and X-ray crystallography, we established that the DcpS substrate length-sensing mechanism is based on steric clashes between the enzyme and the third nucleotide of a capped mRNA. For longer mRNA substrates, these clashes prevent conformational changes in DcpS that are required for the formation of a catalytically competent active site. Point mutations that enlarge the space for the third nucleotide in the mRNA body enhance the activity of DcpS on longer mRNA species. We find that this mechanism to ensure that the enzyme is not active on translating long mRNAs is conserved from yeast to humans. Finally, we show that the products that the exosome releases after 3′ to 5′ degradation of the mRNA body are indeed short enough to be decapped by DcpS. Our data thus directly confirms the notion that mRNA products of the exosome are direct substrates for DcpS. In summary, we demonstrate a direct relationship between conformational changes and enzyme activity that is exploited to achieve substrate selectivity.

Decapping scavenger enzymes (DcpSs) are important players in mRNA degradation machinery and conserved in eukaryotes. Importantly, human DcpS is the recognized target for spinal muscular atrophy (SMA) and acute myeloid leukemia (AML) therapy, and has recently been connected to development of intellectual disability. Most recombinant DcpSs used in biochemical and biophysical studies are prepared as tagged proteins, with polyhistidine (His-tag) at the N-terminus or C-terminus. Our work is the first report on the parallel characterization of three versions of DcpSs (native and N- or C-terminally tagged) of three species (humans, Caenorhabditis elegans, and Ascaris suum). The native forms of all three enzymes were prepared by N-(His)10 tag cleavage. Protein thermal stability, measured by differential scanning fluorimetry (DSF), was unaffected in the case of native and tagged versions of human and A. suum DcpS; however, the melting temperature (Tm) of C. elagans DcpS of was significantly influenced by the presence of the additional N- or C-tag. To investigate the impact of the tag positioning on the catalytic properties of DcpS, we tested the hydrolytic activity of native DcpS and their His-tagged counterparts toward cap dinucleotides (m7GpppG and m32,2,7GpppG) and m7GDP. The kinetic data indicate that dinucleotide substrates are hydrolyzed with comparable efficiency by native human and A. suum DcpS and their His-tagged forms. In contrast, both His-tagged C. elegans DcpSs exhibited higher activity toward m7GpppG than the native enzyme. m7GDP is resistant to enzymatic cleavage by all three forms of human and nematode DcpS.

Enforcing safety in the presence of stochastic uncertainty is a challenging problem. Traditionally, researchers have proposed safety in the statistical mean as a safety measure for systems subject to stochastic uncertainty. However, ensuring safety in the statistical mean is only reasonable if system’s safe behavior in the large number of runs is of interest, which precludes the use of mean safety in practical scenarios. In this letter, we propose a risk sensitive notion of safety called conditional-value-at-risk (CVaR) safety. We introduce CVaR barrier functions as a tool to enforce CVaR-safety and propose conditions for their Boolean compositions. Given a legacy controller, we show that we can design a minimally interfering CVaR-safe controller via solving difference convex programs (DCPs). We elucidate the proposed method by applying it to a bipedal robot locomotion case study.

Dinucleotide analogs of the messenger RNA cap (m7GpppN) are useful research tools and have potential applications as translational inhibitors or reagents for modification of in vitro transcribed mRNAs. It has been previously reported that replacing the methyl group at the N7-position with benzyl (Bn) produces a dinucleotide cap with superior properties. Here, we followed up on this finding by synthesizing 17 novel Bn7GpppG analogs and determining their structure–activity relationship regarding translation and translational inhibition. The compounds were prepared in two steps, including selective N7-alkylation of guanosine 5′-monophosphate by arylmethyl bromide followed by coupling with imidazole-activated GDP, with total yields varying from 22% to 62%. The compounds were then evaluated by determining their affinity for eukaryotic translation initiation factor 4E (eIF4E), testing their susceptibility to decapping pyrophosphatase, DcpS—which is most likely the major cellular enzyme targeting this type of compound—and determining their translation inhibitory properties in vitro. We also synthesized mRNAs capped with the evaluated compounds and tested their translational properties in A549 cells. Our studies identified N7-(4-halogenbenzyl) substituents as promising modifications in the contexts of either mRNA translation or translational inhibition. Finally, to gain more insight into the consequences at the molecular level of N7-benzylation of the mRNA cap, we determined the crystal structures of three compounds with eIF4E.

mRNA degradation is a key mechanism of gene expression regulation. In the 3′ → 5′ decay pathway, mRNA is degraded by the exosome complex and the resulting cap dinucleotide or short-capped oligonucleotide is hydrolyzed mainly by a decapping scavenger enzyme (DcpS)—a member of the histidine triad family. The decapping mechanism is similar for DcpS from different species; however, their respective substrate specificities differ. In this paper, we describe experiments exploring DcpS activity from human (hDcps), Caenorhabditis elegans (CeDcpS), and Ascaris suum (AsDcpS) toward dinucleotide cap analogues modified at the N2 position of 7-methylguanosine. Various alkyl substituents were tested, and cap analogues with a longer than three-carbon chain were nonhydrolyzable by hDcpS and CeDcpS. Resistance of the modified cap analogues to hDcpS and CeDcpS may be associated with their weaker binding with enzymes.

Graphical abstract In the past few decades, nanotechnology has been employed to provide breakthroughs in the diagnosis and treatment of several diseases using drug-carrying particles (DCPs). In such an endeavor, the optimal design of DCPs is paramount, which necessitates the use of an accurate and trustworthy constitutive model in computational fluid dynamics (CFD) simulators. We herein introduce a continuum model for elaborating on the rheological implications of adding particles in blood. The model is developed using non-equilibrium thermodynamics to guarantee thermodynamic admissibility. Red blood cells are modeled as deformed droplets with a constant volume that are able to aggregate, whereas particles are considered rigid spheroids. The model predictions are compared favorably against rheological data for both spherical and non-spherical particles immersed in non-aggregating blood. It is expected that the use of this model will allow for the testing of DCPs in virtual patients and for their tailor-design in treating various diseases. Supplementary Information The online version contains supplementary material available at 10.1007/s00397-021-01289-x.

Drop-carrier particles (DCPs) are solid microparticles designed to capture uniform microscale drops of a target solution without using costly microfluidic equipment and techniques. DCPs are useful for automated and high-throughput biological assays and reactions, as well as single-cell analyses. Surface energy minimization provides a theoretical prediction for the volume distribution in pairwise droplet splitting, showing good agreement with macroscale experiments. We develop a probabilistic pairwise interaction model for a system of such DCPs exchanging fluid volume to minimize surface energy. This leads to a theory for the number of pairwise interactions of DCPs needed to reach a uniform volume distribution. Heterogeneous mixtures of DCPs with different sized particles require fewer interactions to reach a minimum energy distribution for the system. We optimize the DCP geometry for minimal required target solution and uniformity in droplet volume.

The liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.

Homozygous mutations in the gene encoding the scavenger mRNA-decapping enzyme, DcpS, have been shown to underlie developmental delay and intellectual disability. Intellectual disability is associated with both abnormal neocortical development and mRNA metabolism. However, the role of DcpS and its scavenger decapping activity in neuronal development is unknown. Here, we show that human neurons derived from patients with a DcpS mutation have compromised differentiation and neurite outgrowth. Moreover, in the developing mouse neocortex, DcpS is required for the radial migration, polarity, neurite outgrowth, and identity of developing glutamatergic neurons. Collectively, these findings demonstrate that the scavenger mRNA decapping activity contributes to multiple pivotal roles in neural development and further corroborate that mRNA metabolism and neocortical pathologies are associated with intellectual disability.

Introduction Health behaviours result in oral health problems. Behaviour change techniques, informed by behaviour science, are rarely utilised by dental care professionals (DCPs) within routine care.Aim To develop a theory-informed intervention to support DCPs' behaviour change conversations and evaluate its feasibility and acceptability.Intervention A behaviour change toolkit (Toothpicks) comprising 33 behaviour change techniques relevant to dentistry, delivered within an interactive online course.Design Development and mixed-methods evaluation of the intervention.Materials and methods Participants' motivation to discuss behaviour change with patients was measured before and after training using a validated questionnaire. Acceptability was assessed through semi-structured interviews.Results DCPs' (N = 32) motivation increased significantly post-training. Participants found the training acceptable and reported subsequently implementing techniques into their practice. Potential barriers preventing implementation to clinical practice include perceived lack of opportunities to effect change within the constraints of the clinical context.Conclusions Acceptable theory-informed training that is acceptable and accessible can be developed that increases DCPs' motivation to discuss behaviour change with patients. Further research is necessary to establish the longer-term impact of brief behaviour change training on DCPs' clinical practice and patient health behaviours.

The aim of the study was to evaluate the plasma levels of vitamin K (VK), prothrombin, des-γ-carboxyprothrombin (DCP) by ELISA with two types of monoclonal antibodies (MU-3 and 19B7), and urinary γ-carboxyglutamic acid (γ-Gla) in healthy adults (45 males and 45 females) and 11 patients with liver cirrhosis. VK and γ-Gla were analyzed by reverse-phase HPLC, prothrombin was determined using a method with a synthetic chromogenic substrate, and DCPs were analyzed by immunoaffinity chromatography and reverse-phase HPLC, and measured by ELISA. We were able to detect phylloquinone K (PK) and menaquinones MK-4, -5, -6, -7, -8 and -9, and we isolated several DCPs from plasma. Age had significant positive correlations with levels of urinary γ-Gla, plasma MK-7 and total VK, and VKDPs (prothrombin and DCP using MU-3 antibody) in the healthy adults. Significant positive correlations were also found between urinary γ-Gla and plasma levels of PK, MK-4, MK-7, and total VK and VKDPs (prothrombin and DCP using MU-3 antibody) in the healthy adults. γ-Gla and total VK levels were significantly higher in healthy adults than in patients with liver cirrhosis, and VK components, prothrombin, DCPs, and the MU-3/19B7 ratio showed a tendency to be higher in the healthy adults. We conclude that the status of VK and related proteins may reflect the latent increase in des-γ-carboxylation in healthy aging.

Recent control plane solutions in a software-defined network (SDN) setting assume physically distributed but logically centralized control instances: a distributed control plane (DCP). As networks become more heterogeneous with increasing amount and diversity of network resources, DCP deployment strategies must be both fast and flexible to cope with varying network conditions whilst fulfilling constraints. However, many approaches are too slow for practical applications and often address only bandwidth or delay constraints, while control-plane reliability is overlooked and control-traffic routability is not guaranteed. We demonstrate the capabilities of our optimization framework [1]-[3] for fast deployment of DCPs, guaranteeing routability in line with control service reliability, bandwidth and latency requirements. We show that our approach produces robust deployment plans under changing network conditions. Compared to state of the art solvers, our approach is magnitudes faster, enabling deployment of DCPs within minutes and seconds, rather than days and hours. Time Critical Clouds Celtic Plus 5G-PERFECTA

The private sector of Ghana faces many problems with respect to raising capital for their operations; this is largely due to government relying heavily on the local credit market for funds for developmental projects. This study uses exponential smoothing method (ESM) in EViews to build a single sample model to forecast future domestic credit to private sector (DCPS) values in Ghana. Secondary annual data on DCPS spanning the period from 1982 to 2016 is used. The findings show that an exponential smoothing model with multiplicative error, additive trend and no seasonality fits the data best. The model had very small residual measures, which demonstrates a good model for forecasting. The estimated model is used to forecast the DCPS values for Ghana from the year 2017 to 2020. The results of this study will help private business people plan for the future. The results will also help policy makers to make informed decisions and formulate policies to improve the DCPS figures, since the private sector is the engine of growth, and crowding out would not be in the best interest of the government and the nation as a whole.

mRNA decapping proteins (DCPs) are components of the P-bodies in the cell which are hubs of mRNAs targeted for decay and they provide the cell with a reversible pool of mRNAs in response to cellular demands. TheDrosophilagenome codes for two decapping proteins, DCP1 and DCP2 out of which DCP2 is the cognate decapping enzyme. The present endeavour explores the endogenous promoter firing, transcript and protein expression ofDCP2inDrosophilawherein, besides a ubiquitous expression across development, we identify active expression paradigm during dorsal closure and a plausible moonlighting expression in the Corazonin neurons of the larval brain. We also demonstrate that the ablation ofDCP2leads to embryonic lethality and defects in vital morphogenetic processes whereas a knockdown ofDCP2in the Corazonin neurons reduces the sensitivity to ethanol in adults, thereby ascribing novel regulatory roles to DCP2. Our findings unravel novel putative roles for DCP2 and identify it as a candidate for studies on the regulated interplay of essential molecules during early development inDrosophila, nay the living world.

Dihalophenols such as dichlorophenols (DCPs) are important industrial chemical intermediates, but also persistent pollutants in the environment. Oxidative dehalogenation by microbes is an efficient biological method to degrade halophenols, but the mechanism is unclear yet. Cupriavidus nantongensis X1T was a type strain of genus Cupriavidus, and could degrade 2,4-dichlorophenol of 50 mg/L within 12 h. The degradation rate constant was approximately 84 fold greater than that by Bacillus endophyticus CP1R43, a well-studied 2,4-DCP-degrading bacterial strain. The genes encoding 2,4,6-trichlorophenol monooxygenase (TcpA) and NAD(P)H:FAD reductase (Fre) from strain X1T were cloned and expressed. The expressed TcpA Fre were purified. The molecular docking of TcpA with DCPs and point mutation experiments showed that the degradation activity of TcpA was associated with the length of the hydrogen bond between the substrates and the amino acids in the active pocket. DCPs were degraded via a stepwise oxidative dechlorination in a positive relationship between the oxidation ability and the electron-withdrawing potential of the p-position group. In addition, TcpA has dual dehalogenation and denitration functions. The results demonstrate that either strain X1T or TcpA and Fre can effectively dehalogenate dihalophenols, which can be useful for the treatment of dihalophenols in wastewaters and remediation of DCP-contaminated environments.

Messenger RNA (mRNA) is the working copy of a gene containing the information for the production of a specific protein. The amount of any given protein has to be adjusted to the current needs of a cell. One mechanism for the regulation of protein production is the targeted degradation of the corresponding mRNA. A key element of an mRNA molecule is its 5’ cap structure that serves as a binding hub for interacting proteins and as a protection against premature degradation. During regulated mRNA degradation, the RNA body can be degraded by the exosome complex from the 3’ end, which leaves short capped RNA fragments. The cap structure of these fragments is removed by the Scavenger Decapping Enzyme (DcpS). This dimeric enzyme has a bipartite active site which is constituted from residues of two domains. Substrate binding induces a see-saw like conformational change that closes the active site around the substrate. In this thesis, we show that this domain motion is essential for the catalytic activity of DcpS, but that under substrate excess these motions can be too fast to allow for efficient substrate turnover, resulting in a unique way of substrate inhibition. To date, the information on the structure and protein dynamics of DcpS during catalysis rely on the usage of cap analogues, representing only the cap structure itself and one nucleotide of the RNA body. The products of the exosomal degradation of mRNA and thus substrates of DcpS, however, are short capped RNA fragments. The synthesis of such capped RNA was not possible until now, and we therefore established a method for the large scale enzymatic capping of in vitro transcribed RNA that employs the capping enzyme of vaccinia virus. This allows us to produce homogeneous, capped RNA of different length enabling in-depth biochemical and biophysical studies of the DcpS enzyme. Activity assays of DcpS with capped RNA of different lengths showed a clear influence of substrate length on catalytic activity with a strong preference for substrates of up to two nucleotides. We show that longer RNA is incompatible with the catalytically required domain motions of DcpS, due to steric hindrance between the enzyme and the mRNA body. We show that the preference of DcpS for capped mono- and di-nucleotides is conserved in various species and that this length dependence is in accordance with our preliminary data on the product length of the exosome. From this we conclude that the biological function of the threshold in substrate usage of DcpS is based on a direct handover of RNA fragments from the exosome to DcpS to prevent the decapping of actively translated transcripts. Messenger RNA (mRNA) ist die Arbeitskopie eines Gens, welche die Information zur Herstellung eines spezifischen Proteins trägt. Die Menge eines jeden Proteins muss an den ständig wechselnden Bedarf einer Zelle angepasst werden. Ein Mechanismus, die Proteinproduktion zu regulieren, ist der gezielte Abbau der entsprechenden mRNA. Ein wichtiges Element eines mRNA Moleküls ist seine 5‘-Cap-Struktur, welche als Plattform für Protein-Interaktionen, sowie als Schutz vor vorzeitigem Abbau dient. Während des regulierten Abbaus der mRNA, kann der RNA-Körper durch den Exosom-Komplex vom 3‘-Ende her abgebaut werden, was in kurzen gecappten RNA-Fragmenten resultiert. Die Cap-Struktur dieser Fragmente wird durch das Scavenger Decapping Enzym (DcpS) entfernt. Das dimere Enzym besitzt ein zweigeteiltes aktives Zentrum, welches sich aus Resten zweier Domänen zusammensetzt. Durch Substratbindung wird eine wippenartige Konformationsänderung ausgelöst, welche das aktive Zentrum um das Substrat schließt. Wir zeigen, dass diese Bewegung der Domänen für die katalytische Aktivität von DcpS essentiell ist. Allerdings kann die Bewegung unter Substratüberschuss zu schnell sein, um effektiven Substratumsatz zu gestatten, was in einer einzigartigen Weise der Substrat-Inhibierung resultiert. Bis heute beruhen alle Informationen über Struktur und Dynamik von DcpS auf Cap-Analoga, welche lediglich die Cap-Struktur selbst und das erste Nucleotid des RNA-Körpers repräsentieren. Allerdings sind die Produkte des exosomalen Abbaus der mRNA, und damit die Substrate von DcpS, kurze gecappte RNA-Fragmente. Da die Synthese solcher gecappter RNA bislang nicht möglich war, haben wir eine Methode für das enzymatische Capping von in vitro transkribierter RNA in großem Maßstab, beruhend auf dem Capping Enzym des Vaccinia Virus, entwickelt. Diese erlaubt es uns, homogene, gecappte RNA unterschiedlicher Länge herzustellen, welche eingehende biochemische und biophysikalische Untersuchungen des DcpS-Enzyms ermöglicht. Aktivitäts-Assays von DcpS mit gecappter RNA unterschiedlicher Länge zeigen einen klaren Einfluss der Substratlänge auf die katalytische Aktivität mit starker Präferenz für Substrate von bis zu zwei Nukleotiden. Wir zeigen, dass längere RNA die Bewegung der Domänen, welche für die erfolgreiche Katalyse notwendig ist, nicht induziert. Aus Strukturdaten können wir schließen, dass der Schließmechanismus des aktiven Zentrums aufgrund eines längerer RNA-Körpers sterisch behindert wird. Die Untersuchung von Enzymen verschiedener Spezies ergibt, dass die Länge der effektiv umgesetzten Substrate und die strukturelle Grundlage für die Substrat-Präferenz speziesunabhängig konserviert sind. Die Präferenz für gecappte Mono- und Dinukleotide von DcpS stimmt mit unseren vorläufigen Daten für die Länge der Exosom-Produkte überein. Daraus schließen wir, dass die biologische Funktion der Beschränkung von DcpS auf kurze Substrate auf einer direkten Übergabe von RNA-Fragmenten von Exosom zu DcpS beruht. Dies verhindert, dass von Transkripten, welche aktiv translatiert werden, die Cap-Struktur durch DcpS entfernt wird.

Catalytic wet peroxide oxidation (CWPO) of dichlorophenols (DCPs) over Fe-Cu-pillared clay (PILC) without and with NaCl was investigated. Concentration change dynamics in H2O2, Cl−, and hyd...

Host nucleases are implicated in antiviral response through the processing of pathogen-derived nucleic acids. Among many host RNases, decapping enzymes DCP1 and 2, and 5′→3′ exonuclease XRN1, which are components of the RNA decay machinery, have been extensively studied in prokaryotes, plants, and invertebrates but less so in mammalian systems. As a result, the implication of XRN1 and DCPs in viral replication, in particular, the spatio-temporal dynamics during RNA viral infections remains elusive. Here, we highlight that XRN1 and DCPs play a critical role in limiting several groups of RNA viral infections. This antiviral activity was not obvious in wild-type cells but clearly observed in type I interferon (IFN-I)-deficient cells. Mechanistically, infection with RNA viruses induced the enrichment of XRN1 and DCPs in viral replication complexes (vRCs), hence forming distinct cytoplasmic aggregates. These aggregates served as sites for direct interaction between XRN1, DCP1/2, and viral ribonucleoprotein that contains viral RNA (vRNA). Although these XRN1-DCP1/2-vRC-containing foci resemble antiviral stress granules (SGs) or P-body (PB), they did not colocalize with known SG markers and did not correlate with critical PB functions. Furthermore, the presence of 5′ mono- and 5′ triphosphate structures on vRNA was not required for the formation of XRN1-DCP1/2-vRC-containing foci. On the other hand, single-, double-stranded, and higher-ordered vRNA species play a role but are not deterministic for efficient formation of XRN1-DCP1/2 foci and consequent antiviral activity in a manner proportional to RNA length. These results highlight the mechanism behind the antiviral function of XRN1-DCP1/2 in RNA viral infections independent of IFN-I response, protein kinase R and PB function.

Eukaryotic mRNAs are modified at their 5′ end early during transcription by the addition of N7-methylguanosine (m7G), which forms the “cap” on the first 5′ nucleotide. Identification of the 5′ nucleotide on mRNA is necessary for determination of the Transcription Start Site (TSS). We explored the effect of various reaction conditions on the activity of the yeast scavenger mRNA decapping enzyme DcpS and examined decapping of 30 chemically distinct cap structures varying the state of methylation, sugar, phosphate linkage, and base composition on 25mer RNA oligonucleotides. Contrary to the generally accepted belief that DcpS enzymes only decap short oligonucleotides, we found that the yeast scavenger decapping enzyme decaps RNA transcripts as long as 1400 nucleotides. Further, we validated the application of yDcpS for enriching capped RNA using a strategy of specifically tagging the 5′ end of capped RNA by first decapping and then recapping it with an affinity-tagged guanosine nucleotide.

Eukaryotic mRNAs are modified at their 5’ end early during transcription by the addition ofN7-methylguanosine (m7G), which forms the “cap” on the first 5’ nucleotide. Identification of the 5’ nucleotide on mRNA is necessary for determination of the Transcription Start Site (TSS). We explored the effect of various reaction conditions on the activity of the yeast scavenger mRNA decapping enzyme DcpS (yDcpS) and examined decapping of 30 chemically distinct cap structures varying the state of methylation, sugar, phosphate linkage, and base composition on 25mer RNA oligonucleotides. Contrary to the generally accepted belief that DcpS enzymes only decap short oligonucleotides, we found that yDcpS efficiently decaps RNA transcripts as long as 1400 nucleotides. Further, we validated the application of yDcpS for enriching capped RNA using a strategy of specifically tagging the 5’ end of capped RNA by first decapping and then recapping it with an affinity-tagged guanosine nucleotide.

The mRNA 5&prime, cap consists of N7-methylguanosine bound by a 5&prime, 5&prime, triphosphate bridge to the first nucleotide of the transcript. The cap interacts with various specific proteins and participates in all key mRNA-related processes, which may be of therapeutic relevance. There is a growing demand for new biophysical and biochemical methods to study cap&ndash, protein interactions and identify the factors which inhibit them. The development of such methods can be aided by the use of properly designed fluorescent molecular probes. Herein, we synthesized a new class of m7Gp3G cap derivatives modified with an alkyne handle at the N1-position of guanosine and, using alkyne-azide cycloaddition, we functionalized them with fluorescent tags to obtain potential probes. The cap derivatives and probes were evaluated in the context of two cap-binding proteins, eukaryotic translation initiation factor (eIF4E) and decapping scavenger (DcpS). Biochemical and biophysical studies revealed that N1-propargyl moiety did not significantly disturb cap&ndash, protein interaction. The fluorescent properties of the probes turned out to be in line with microscale thermophoresis (MST)-based binding assays.

In practice, teacher turnover appears to have negative effects on school quality as measured by student performance. However, some simulations suggest that turnover can instead have large positive effects under a policy regime in which low-performing teachers can be accurately identified and replaced with more effective teachers. This study examines this question by evaluating the effects of teacher turnover on student achievement under IMPACT, the unique performance-assessment and incentive system in the District of Columbia Public Schools (DCPS). Employing a quasi-experimental design based on data from the first years of IMPACT, we find that, on average, DCPS replaced teachers who left with teachers who increased student achievement by 0.08 standard deviation ( SD) in math. When we isolate the effects of lower-performing teachers who were induced to leave DCPS for poor performance, we find that student achievement improves by larger and statistically significant amounts (i.e., 0.14 SD in reading and 0.21 SD in math). In contrast, the effect of exits by teachers not sanctioned under IMPACT is typically negative but not statistically significant.

Fiona Ellwood et al, 2016 explore dental care professionals' (DCPs') awareness of mentorship and clinical governance as part of a local professional development programme

Background Studies examining the impact of training modules on characterization of diminutive colonic polyps (DCP) show varying results. Aim We aimed to assess the impact of a novel web-based training module on the accuracy of in vivo characterization of DCPs using different imaging modalities. Differences between groups with varying degrees of endoscopic experience were also assessed. Methods In total, 90 images of 30 DCPs viewed with high definition white light (HDWL), i-Scan, and indigo carmine chromoendoscopy were included in an online test module. Testing was undertaken before and after completing a novel web-based in vivo characterization training module. In total, 21 subjects (medical students (MS), gastroenterology trainees (GT), and gastroenterology consultants (GC)) undertook the tests and training module. Results No statistically significant difference in overall accuracy was found between the three groups either pre- (MS 59.1 %, GR 65.7 %, GC 62.4 %, P = ns for all three comparisons) or post-training (MS 69.2 %, GR 71.1 %, GC 71.3 %, P = ns for all three comparisons). Accuracy improved significantly for all three groups post-training (P Conclusions Skills for in vivo characterization of DCPs are not acquired through endoscopic experience alone. A novel web-based training intervention results in modest improvements in accuracy with further improvements likely to require more prolonged training.

A polyomino is a finite, edge-connected set of cells in the plane. At the present time, an enumeration of all polyominoes is nowhere in sight. On the other hand, there are several subsets of polyominoes for which generating functions are known. For example, there exists extensive knowledge about column-convex polyominoes, a model introduced by Temperley in 1956. While studying column-convex polyominoes, researchers also gave a look at diagonally convex polyominoes (DCPs), but noticed an awkward feature: when the last diagonal of a DCP is deleted, the remaining object is not always a polyomino. So researchers focused their attention on directed DCPs. (A directed DCP is such a DCP that remains a polyomino when, for any $i$, its last $i$ diagonals are deleted.) Directed DCPs gradually became well understood, whereas general DCPs have remained unexplored up to now. In this paper, we finally face general DCPs. Modulo a little trick, which saves us from dealing with non-polyominoes, we use the layered approach (described in chapter 3 of the book ``Polygons, Polyominoes and Polycubes", edited by Anthony Guttmann). The computations are of remarkable bulk. Our main result is the perimeter generating function for DCPs; we denote it $D(d,x)$. The function $D(d,x)$ is algebraic and satisfies an equation of degree eight. The formula for $D(d,x)$ is about eight pages long. That formula involves nine polynomials in $d$ and $x$, and each of those polynomials is of degree $58$ or more in $x$. The interested reader can view the formula for $D(d,x)$ in the Maple worksheet attached to this paper., Comment: 17 pages, 9 figures

International audience; Synthetic delivery systems that are described as smart are considered essential for the successful development of gene therapies. Dynamic covalent polymers (DCP) are dynamic and adaptive species that can expand and shorten their main chain in a reversible fashion. In particular, polyacylhydrazone DCPs are pH-sensitive and undergo hydrolytic dissociation at acidic pH, which is an interesting feature for gene delivery. Building upon our previous finding that cationic DCPs can complex DNA through multivalent interactions, we report here on a new generation of DCPs that incorporate modified amino acids. The covalent self-assembly through polycondensation was extended towards multifunctional DCPs combining different building blocks and different molecular dynamics. These biomolecular DCPs were found able to complex both long DNA and siRNA, and biological studies demonstrate that they are able to deliver functional siRNA in living cells. This straightforward and modular approach to the self-production of multifunctional and biomolecular DCPs as siRNA vectors can therefore constitute a stepping stone in smart gene delivery using dynamic and adaptive biodynamers.

The Dental Professional's Conference (DPC) 2018 brought together Dental Professionals from across all the clinical and technical disciplines. Daniel Shaw provides an overview.