...research translation is needed. ...powerful leadership must continue and must include articulate advocacy for the im- portance of health in building and redevelopment decisions.
Internal ribosome entry sites/segments (IRESs) were first discovered over 20 years ago in picornaviruses, followed by the discovery of two other types of IRES in hepatitis C virus (HCV), and the ...dicistroviruses, which infect invertebrates. In the meantime, reports of IRESs in eukaryotic cellular mRNAs started to appear, and the list of such putative IRESs continues to grow to the point in which it now stands at ~100, 80% of them in vertebrate mRNAs. Despite initial skepticism from some quarters, there now seems universal agreement that there is genuine internal ribosome entry on the viral IRESs. However, the same cannot be said for cellular mRNA IRESs, which continue to be shrouded in controversy. The aim of this article is to explain why vertebrate mRNA IRESs remain controversial, and to discuss ways in which these controversies might be resolved.
We report the synthesis of a stable analogue of τ-phosphohistidine: 4-phosphopyrazol-2-yl alanine (pPza). Polyclonal antibodies generated against the mimic show high reactivity and selectivity for ...τ-phosphohistidine, with minor or no cross-reactivity towards non-phosphorylated histidine or O-phosphoamino acids, including phosphotyrosine.
ObjectivesWe sought to use natural language processing to develop a suite of language models to capture key symptoms of severe mental illness (SMI) from clinical text, to facilitate the secondary use ...of mental healthcare data in research.DesignDevelopment and validation of information extraction applications for ascertaining symptoms of SMI in routine mental health records using the Clinical Record Interactive Search (CRIS) data resource; description of their distribution in a corpus of discharge summaries.SettingElectronic records from a large mental healthcare provider serving a geographic catchment of 1.2 million residents in four boroughs of south London, UK.ParticipantsThe distribution of derived symptoms was described in 23 128 discharge summaries from 7962 patients who had received an SMI diagnosis, and 13 496 discharge summaries from 7575 patients who had received a non-SMI diagnosis.Outcome measuresFifty SMI symptoms were identified by a team of psychiatrists for extraction based on salience and linguistic consistency in records, broadly categorised under positive, negative, disorganisation, manic and catatonic subgroups. Text models for each symptom were generated using the TextHunter tool and the CRIS database.ResultsWe extracted data for 46 symptoms with a median F1 score of 0.88. Four symptom models performed poorly and were excluded. From the corpus of discharge summaries, it was possible to extract symptomatology in 87% of patients with SMI and 60% of patients with non-SMI diagnosis.ConclusionsThis work demonstrates the possibility of automatically extracting a broad range of SMI symptoms from English text discharge summaries for patients with an SMI diagnosis. Descriptive data also indicated that most symptoms cut across diagnoses, rather than being restricted to particular groups.
Language is powerful and can have a strong impact on perceptions as well as behavior. A task force, consisting of representatives from the American Association of Diabetes Educators (AADE) and the ...American Diabetes Association (ADA), convened to discuss language in diabetes care and education. This document represents the expert opinion of the task force. The literature supports the need for a language movement in diabetes care and education. There are effective ways of communicating about diabetes. This article provides recommendations for language used by health care professionals and others when discussing diabetes through spoken or written words-whether directed to people with diabetes, colleagues, or the general public, as well as research questions related to language and diabetes.
Translation termination in eukaryotes occurs in response to a stop codon in the ribosomal A-site and requires two release factors (RFs), eRF1 and eRF3, which bind to the A-site as an eRF1/eRF3/GTP ...complex with eRF1 responsible for codon recognition. After GTP hydrolysis by eRF3, eRF1 triggers hydrolysis of the polypeptidyl-tRNA, releasing the completed protein product. This leaves an 80S ribosome still bound to the mRNA, with deacylated tRNA in its P-site and at least eRF1 in its A-site, which needs to be disassembled and released from the mRNA to allow further rounds of translation. The first step in recycling is dissociation of the 60S ribosomal subunit, leaving a 40S/deacylated tRNA complex bound to the mRNA. This is mediated by ABCE1, which is a somewhat unusual member of the ATP-binding cassette family of proteins with no membrane-spanning domain but two essential iron-sulfur clusters. Two distinct pathways have been identified for subsequent ejection of the deacylated tRNA followed by dissociation of the 40S subunit from the mRNA, one executed by a subset of the canonical initiation factors (which therefore starts the process of preparing the 40S subunit for the next round of translation) and the other by Ligatin or homologous proteins. However, although this is the normal sequence of events, there are exceptions where the termination reaction is followed by reinitiation on the same mRNA (usually) at a site downstream of the stop codon. The overwhelming majority of such reinitiation events occur when the 5'-proximal open reading frame (ORF) is short and can result in significant regulation of translation of the protein-coding ORF, but there are also rare examples, mainly bicistronic viral RNAs, of reinitiation after a long ORF. Here, we review our current understanding of the mechanisms of termination, ribosome recycling, and reinitiation after translation of short and long ORFs.
Migration to two mines in Laos Jackson, Richard T.
Sustainable development (Bradford, West Yorkshire, England),
September/October 2018, Letnik:
26, Številka:
5
Journal Article
Recenzirano
This paper considers migration patterns to the Sepon and Phu Kham copper‐gold mining projects in Laos. Data collected biennially at these two mining ventures to monitor socio‐economic change is ...analysed to establish numbers, sources and types of migrants towards these mines and the distribution of project‐generated cash flows captured by such groups in comparison with those accruing to pre‐existing populations. The bulk of migration is demonstrated to be due to personal ties between migrants and pre‐existing residents. It is argued that in‐migration ultimately tends to dilute and partly undermine the immediate and positive impact of any intentional efforts to maximize local economic opportunities. Efforts to maximize employment for pre‐existing populations are shown to have been significantly undermined by numerous factors. Variations between different state policies on the distribution of and eligibility for receipt of project benefits are key to determining the extent of inward migration. The mines considered here, like many such operations elsewhere and throughout history, are located in relatively remote areas where the prospects for any form of economic development, other than mining, have been minimal. It is unlikely, therefore, that the higher levels of income and the increased opportunities (both social and economic) generated in mine impact areas during operations will be maintained after mine closure. The challenge to mining companies (and host governments) is not so much to create a sustainable economy in the places where they operate but rather to create sustainable improvements in the opportunities for the people who were living in such places prior to the start of their operations.
Protein–protein interfaces are highly attractive targets for drug discovery because they are involved in a large number of disease pathways where therapeutic intervention would bring widespread ...benefit. Recent successes have challenged the widely held belief that these targets are ‘undruggable’. The pocket finding algorithms described here show marked differences between the binding pockets that define protein–protein interactions (PPIs) and those that define protein–ligand interactions (PLIs) of currently marketed drugs. In the case of PPIs, drug discovery methods that simultaneously target several small pockets at the protein–protein interface are likely to increase the chances of success in this new and important field of therapeutics.
This paper presents a new and widely applicable nonparametric approach to the characterisation of time series dynamics. The approach involves analysis of the incidence of occurrence of patterns in ...the direction of movement of the series, and may readily be applied to time series data measured on any scale. The paper includes derivations of analytic forms for two (infinite) families of distributions under the null hypothesis of random behaviour, and of a useful analytic form for the generation of the moments of these distributions. The distributions are asymptotically normal, so allowing for straightforward application of the approach presented in the paper too long series of high frequency and/or extended time period data. Areas of application in finance and accounting are suggested.
Abstract
Background
The 16S rRNA gene is used extensively in bacterial phylogenetics, in species delineation, and now widely in microbiome studies. However, the gene suffers from intragenomic ...heterogeneity, and reports of recombination and an unreliable phylogenetic signal are accumulating. Here, we compare core gene phylogenies to phylogenies constructed using core gene concatenations to estimate the strength of signal for the 16S rRNA gene, its hypervariable regions, and all core genes at the intra- and inter-genus levels. Specifically, we perform four intra-genus analyses (
Clostridium
,
n
= 65;
Legionella
,
n
= 47;
Staphylococcus
,
n
= 36; and
Campylobacter
,
n
= 17) and one inter-genus analysis 41 core genera of the human gut microbiome (31 families, 17 orders, and 12 classes),
n
= 82.
Results
At both taxonomic levels, the 16S rRNA gene was recombinant and subject to horizontal gene transfer. At the intra-genus level, the gene showed one of the lowest levels of concordance with the core genome phylogeny (50.7% average). Concordance for hypervariable regions was lower still, with entropy masking providing little to no benefit. A major factor influencing concordance was SNP count, which showed a positive logarithmic association. Using this relationship, we determined that 690 ± 110 SNPs were required for 80% concordance (average 16S rRNA gene SNP count was 254). We also found a wide range in 16S-23S-5S rRNA operon copy number among genomes (1–27). At the inter-genus level, concordance for the whole 16S rRNA gene was markedly higher (73.8% — 10th out of 49 loci); however, the most concordant hypervariable regions (V4, V3-V4, and V1-V2) ranked in the third quartile (62.5 to 60.0%).
Conclusions
Ramifications of a poor phylogenetic performance for the 16S rRNA gene are far reaching. For example, in addition to incorrect species/strain delineation and phylogenetic inference, it has the potential to confound community diversity metrics if phylogenetic information is incorporated — for example, with popular approaches such as Faith’s phylogenetic diversity and UniFrac. Our results highlight the problematic nature of these approaches and their use (along with entropy masking) is discouraged. Lastly, the wide range in 16S rRNA gene copy number among genomes also has a strong potential to confound diversity metrics.
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