Towards the identification of essential genes using targeted genome sequencing and comparative analysis

BACKGROUND: The identification of genes essential for survival is of theoretical importance in the understanding of the minimal requirements for cellular life, and of practical importance in the identification of potential drug targets in novel pathogens. With the great time and expense required for experimental studies aimed at constructing a catalog of essential genes in a given organism, a computational approach which could identify essential genes with high accuracy would be of great value. RESULTS: We gathered numerous features which could be generated automatically from genome sequence data and assessed their relationship to essentiality, and subsequently utilized machine learning to construct an integrated classifier of essential genes in both S. cerevisiae and E. coli. When looking at single features, phyletic retention, a measure of the number of organisms an ortholog is present in, was the most predictive of essentiality. Furthermore, during construction of our phyletic retention feature we for the first time explored the evolutionary relationship among the set of organisms in which the presence of a gene is most predictive of essentiality. We found that in both E. coli and S. cerevisiae the optimal sets always contain host-associated organisms with small genomes which are closely related to the reference. Using five optimally selected organisms, we were able to improve predictive accuracy as compared to using all available sequenced organisms. We hypothesize the predictive power of these genomes is a consequence of the process of reductive evolution, by which many parasites and symbionts evolved their gene content. In addition, essentiality is measured in rich media, a condition which resembles the environments of these organisms in their hosts where many nutrients are provided. Finally, we demonstrate that integration of our most highly predictive features using a probabilistic classifier resulted in accuracies surpassing any individual feature. CONCLUSION: Using features obtainable directly from sequence data, we were able to construct a classifier which can predict essential genes with high accuracy. Furthermore, our analysis of the set of genomes in which the presence of a gene is most predictive of essentiality may suggest ways in which targeted sequencing can be used in the identification of essential genes. In summary, the methods presented here can aid in the reduction of time and money invested in essential gene identification by targeting those genes for experimentation which are predicted as being essential with a high probability

Effect of Silicon Content on Carbide Precipitation and Low-Temperature Toughness of Pressure Vessel Steels

Cr – Mn – Mo – Ni pressure vessel steels containing 0.54 and 1.55% Si are studied. Metallographic and fractographic analyses of the steels after tempering at 650 and 700°C are performed. The impact toughness at – 30°C and the hardness of the steels are determined. The mass fraction of the carbide phase in the steels is computed with the help of the J-MatPro 4.0 software

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Sensing Senses: Tactile Feedback for the Prevention of Decubitus Ulcers

Decubitus ulcers, also known as pressure sores, is a major problem in health care, in particular for patients with spinal cord injuries. These patients cannot feel the discomfort that would urge healthy people to change their posture. We describe a system that uses a sensor mat to detect problematic postures and provides tactile feedback to the user. The results of our preliminary study with healthy subjects show that the tactile feedback is a viable option to spoken feedback. We envision the system being used for rehabilitation games, but also for everyday Decubitus ulcers prevention

Multiple primary malignancies and subtle mucocutaneous lesions associated with a novel PTEN gene mutation in a patient with Cowden syndrome: Case report

<p>Abstract</p> <p>Background</p> <p>Cowden syndrome (CS) is a cancer predisposition syndrome associated with increased risk of breast, thyroid, and endometrial cancers, and is characterized by development of benign mucocutaneous lesions.</p> <p>Case presentation</p> <p>Here we report on a 58-year-old woman with multiple primary malignancies and subtle mucocutaneous lesions such as small polyps and wart-like papulas. Over a period of 23 years, she developed various malignant neoplasms including thyroid, ovarian, stomach, and colon carcinomas, and a benign meningioma. Direct sequencing analysis of the <it>PTEN </it>gene revealed a novel germline mutation (c.438delT, p.Leu146X).</p> <p>Conclusion</p> <p>This case demonstrates that Cowden syndrome is a multi-system disease that can result in the development of multiple malignant and benign tumors.</p

Increased Resting-State Functional Connectivity in Obese Adolescents; A Magnetoencephalographic Pilot Study

BACKGROUND: Obesity is not only associated with metabolic abnormalities, but also with cognitive dysfunction and changes in the central nervous system. The present pilot study was carried out to investigate functional connectivity in obese and non-obese adolescents using magnetoencephalography (MEG). METHODOLOGY/PRINCIPAL FINDINGS: Magnetoencephalographic recordings were performed in 11 obese (mean BMI 38.8+/-4.6 kg/m(2)) and 8 lean (mean BMI 21.0+/-1.5 kg/m(2)) female adolescents (age 12-19 years) during an eyes-closed resting-state condition. From these recordings, the synchronization likelihood (SL), a common method that estimates both linear and non-linear interdependencies between MEG signals, was calculated within and between brain regions, and within standard frequency bands (delta, theta, alpha1, alpha2, beta and gamma). The obese adolescents had increased synchronization in delta (0.5-4 Hz) and beta (13-30 Hz) frequency bands compared to lean controls (P(delta total) = 0.001; P(beta total) = 0.002). CONCLUSIONS/SIGNIFICANCE: This study identified increased resting-state functional connectivity in severe obese adolescents. Considering the importance of functional coupling between brain areas for cognitive functioning, the present findings strengthen the hypothesis that obesity may have a major impact on human brain function. The cause of the observed excessive synchronization is unknown, but might be related to disturbed motivational pathways, the recently demonstrated increase in white matter volume in obese subjects or altered metabolic processes like hyperinsulinemia. The question arises whether the changes in brain structure and communication are a dynamic process due to weight gain and whether these effects are reversible or not

The relationship between organisational characteristics and the effects of clinical guidelines on medical performance in hospitals, a meta-analysis

We are grateful to our colleagues involved in the systematic review of guideline dissemination and implementation strategies across all settings especially Cynthia Fraser, Graeme MacLennan, Craig Ramsay, Paula Whitty, Martin Eccles, Lloyd Matowe, Liz Shirran. The systematic review of guideline dissemination and implementation strategies across all settings was funded by the UK NHS Health Technology Assessment Program. Dr Ruth Thomas is funded by a Wellcome Training Fellowship in Health Services Research. (Grant number GR063790MA). The Health Services Research Unit is funded by the Chief Scientists Office of the Scottish Executive Department of Health. Dr Jeremy Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake. However the views expressed are those of the authors and not necessarily the funders.Peer reviewedPublisher PD

De novo assembly of Euphorbia fischeriana root transcriptome identifies prostratin pathway related genes

Background Euphorbia fischeriana is an important medicinal plant found in Northeast China. The plant roots contain many medicinal compounds including 12-deoxyphorbol-13-acetate, commonly known as prostratin that is a phorbol ester from the tigliane diterpene series. Prostratin is a protein kinase C activator and is effective in the treatment of Human Immunodeficiency Virus (HIV) by acting as a latent HIV activator. Latent HIV is currently the biggest limitation for viral eradication. The aim of this study was to sequence, assemble and annotate the E. fischeriana transcriptome to better understand the potential biochemical pathways leading to the synthesis of prostratin and other related diterpene compounds. Results In this study we conducted a high throughput RNA-seq approach to sequence the root transcriptome of E. fischeriana. We assembled 18,180 transcripts, of these the majority encoded protein-coding genes and only 17 transcripts corresponded to known RNA genes. Interestingly, we identified 5,956 protein-coding transcripts with high similarity (>=75%) to Ricinus communis, a close relative to E. fischeriana. We also evaluated the conservation of E. fischeriana genes against EST datasets from the Euphorbeacea family, which included R. communis, Hevea brasiliensis and Euphorbia esula. We identified a core set of 1,145 gene clusters conserved in all four species and 1,487 E. fischeriana paralogous genes. Furthermore, we screened E. fischeriana transcripts against an in-house reference database for genes implicated in the biosynthesis of upstream precursors to prostratin. This identified 24 and 9 candidate transcripts involved in the terpenoid and diterpenoid biosyntehsis pathways, respectively. The majority of the candidate genes in these pathways presented relatively low expression levels except for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase (HDS) and isopentenyl diphosphate/dimethylallyl diphosphate synthase (IDS), which are required for multiple downstream pathways including synthesis of casbene, a proposed precursor to prostratin. Conclusion The resources generated in this study provide new insights into the upstream pathways to the synthesis of prostratin and will likely facilitate functional studies aiming to produce larger quantities of this compound for HIV research and/or treatment of patients

Parent and child physical activity and sedentary time: Do active parents foster active children?

<p>Abstract</p> <p>Background</p> <p>Physical activity has many positive effects on children's health while TV viewing has been associated with adverse health outcomes. Many children do not meet physical activity recommendations and exceed TV viewing guidelines. Parents are likely to be an important influence on their children's behaviour. There is an absence of information about the associations between parents' and children's physical activity and TV viewing.</p> <p>Methods</p> <p>Year 6 children and their parent were recruited from 40 primary schools. Results are presented for the 340 parent-child dyads with accelerometer data that met a ≥ 3 day inclusion criteria and the 431 parent-child dyads with complete self-reported TV viewing. Over 80% of the dyads with valid TV viewing data included mothers and their child. Mean minutes of moderate to vigorous physical activity (MVPA), minutes of sedentary time per day and counts per minute were assessed by accelerometer. Self-reported hours of TV viewing were coded into 3 groups (< 2 hours per day, 2-4 hours per day and >4 hours per day. Linear and multi-nominal regression models were run by child gender to examine parent-child associations.</p> <p>Results</p> <p>In linear regression models there was an association for the overall sedentary time of girls and their parents (t = 2.04. p = .020) but there was no association between girls' and parents' physical activity. There were no associations between parents' and boys' sedentary or physical activity time. For girls, the risk of watching more than 4 hours of TV per day, (reference = 2 hours of TV per day), was 3.67 times higher if the girl's parent watched 2-4 hours of TV per day (p = 0.037). For boys, the risk of watching more than 4 hours of TV per day, was 10.47 times higher if the boy's parent watched more than 4 hours of TV per day (p = 0.038).</p> <p>Conclusions</p> <p>There are associations in the sedentary time of parents and daughters. Higher parental TV viewing was associated with an increased risk of high levels of TV viewing for both boys and girls. There were no associations between the time that parents and children spend engaged in physical activity.</p