Statistical modelling of transcript profiles of differentially regulated genes

Background: The vast quantities of gene expression profiling data produced in microarray studies, and the more precise quantitative PCR, are often not statistically analysed to their full potential. Previous studies have summarised gene expression profiles using simple descriptive statistics, basic analysis of variance (ANOVA) and the clustering of genes based on simple models fitted to their expression profiles over time. We report the novel application of statistical non-linear regression modelling techniques to describe the shapes of expression profiles for the fungus Agaricus bisporus, quantified by PCR, and for E. coli and Rattus norvegicus, using microarray technology. The use of parametric non-linear regression models provides a more precise description of expression profiles, reducing the "noise" of the raw data to produce a clear "signal" given by the fitted curve, and describing each profile with a small number of biologically interpretable parameters. This approach then allows the direct comparison and clustering of the shapes of response patterns between genes and potentially enables a greater exploration and interpretation of the biological processes driving gene expression. Results: Quantitative reverse transcriptase PCR-derived time-course data of genes were modelled. "Splitline" or "broken-stick" regression identified the initial time of gene up-regulation, enabling the classification of genes into those with primary and secondary responses. Five-day profiles were modelled using the biologically-oriented, critical exponential curve, y(t) = A + (B + Ct)Rt + ε. This non-linear regression approach allowed the expression patterns for different genes to be compared in terms of curve shape, time of maximal transcript level and the decline and asymptotic response levels. Three distinct regulatory patterns were identified for the five genes studied. Applying the regression modelling approach to microarray-derived time course data allowed 11% of the Escherichia coli features to be fitted by an exponential function, and 25% of the Rattus norvegicus features could be described by the critical exponential model, all with statistical significance of p < 0.05. Conclusion: The statistical non-linear regression approaches presented in this study provide detailed biologically oriented descriptions of individual gene expression profiles, using biologically variable data to generate a set of defining parameters. These approaches have application to the modelling and greater interpretation of profiles obtained across a wide range of platforms, such as microarrays. Through careful choice of appropriate model forms, such statistical regression approaches allow an improved comparison of gene expression profiles, and may provide an approach for the greater understanding of common regulatory mechanisms between genes

The effects on grain quality traits of a grain serpin protein and the VPM 1 segment in southern Australian wheat breeding

Trabalho final do 6º ano médico com vista à atribuição do Grau de Mestre no âmbito do ciclo de estudos de mestrado integrado em medicina da Faculdade de Medicina de Coimbra.Introdução: Estudos prévios estabeleceram que até 12% dos doentes com enfarte agudo do miocárdio não demonstravam lesão coronária aparente ao exame angiográfico. Contudo, existe muito pouca informação disponível acerca deste fenómeno em enfartes agudos do miocárdio sem elevação do segmento ST. O objectivo deste estudo foi avaliar uma população de doentes com esse diagnóstico sujeitos a angiografia coronária, analisando e comparando as características clínicas e os prognósticos entre os que não revelaram lesão coronária aparente e os que apresentavam doença coronária epicárdica. Métodos: O nosso estudo avaliou 270 doentes com enfarte agudo do miocárdio sem elevação do segmento ST que foram sujeitos a angiografia coronária nas primeiras 72 horas de enfarte. Foram valorizadas as características demográficas, clínicas, parâmetros analíticos, achados electrocardiográficos, fracção de ejecção ventricular esquerda, duração do internamento e prognóstico.Previous studies established that up to 12% of patients with acute myocardial infarction did not present coronary atherosclerotic disease demonstrable with angiographic exam. However, little information is available about this phenomenon in acute non-STelevation myocardial infarction. We examined a population of patients with this diagnosis who had undergone coronary angiography, assessing and comparing the clinical characteristics and prognosis between the subset of patients with angiographically normal coronary arteries and the subset of patients with coronary disease

An evaluation of a nurse led unit: an action research study

This study is an exemplar of working in a participatory way with members of the public and health and social care practitioners as co-researchers. A Nurse Consultant Older People working in a nurse-led bed, intermediate care facility in a community hospital acted as joint project lead with an academic researcher. From the outset, members of the public were part of a team of 16 individuals who agreed an evaluation focus and were involved in all stages of the research process from design through to dissemination. An extensive evaluation reflecting all these stakeholders’ preferences was undertaken. Methods included research and audit including: patient and carer satisfaction questionnaire surveys, individual interviews with patients, carers and staff, staff surveys, graffiti board, suggestion box, first impressions questionnaire, patient tracking and a bed census. A key aim of the study has been capacity building of the research team members which has also been evaluated. In terms of impact, the co-researchers have developed research skills and knowledge, grown in confidence, developed in ways that have impacted elsewhere in their lives, developed posters, presented at conferences and gained a better understanding of the NHS. The evaluation itself has provided useful information on the processes and outcomes of intermediate care on the ward which was used to further improve the service

Proper motions, membership, and photometry of open clusters near Eta Carinae

Proper motions and photographic photometry have been derived for nearly 600 stars with 7.5 < V< 15.5 in the region of the very young open clusters Tr 14, Tr 16, and Cr 232 based on 26 plates dating from 1893 to 1990. Cluster membership probabilities have been derived from the proper motions and color-magnitude diagrams of probable members of each cluster are presented. In contrast to a few of the previous studies we find all three clusters to lie at the same distance

piRNA-guided co-transcriptional silencing coopts nuclear export factors.

The PIWI-interacting RNA (piRNA) pathway is a small RNA-based immune system that controls the expression of transposons and maintains genome integrity in animal gonads. In Drosophila, piRNA-guided silencing is achieved, in part, via co-transcriptional repression of transposons by Piwi. This depends on Panoramix (Panx); however, precisely how an RNA binding event silences transcription remains to be determined. Here we show that Nuclear Export Factor 2 (Nxf2) and its co-factor, Nxt1, form a complex with Panx and are required for co-transcriptional silencing of transposons in somatic and germline cells of the ovary. Tethering of Nxf2 or Nxt1 to RNA results in silencing of target loci and the concomitant accumulation of repressive chromatin marks. Nxf2 and Panx proteins are mutually required for proper localization and stability. We mapped the protein domains crucial for the Nxf2/Panx complex formation and show that the amino-terminal portion of Panx is sufficient to induce transcriptional silencing

Hidden Symmetries and Integrable Hierarchy of the N=4 Supersymmetric Yang-Mills Equations

We describe an infinite-dimensional algebra of hidden symmetries of N=4 supersymmetric Yang-Mills (SYM) theory. Our derivation is based on a generalization of the supertwistor correspondence. Using the latter, we construct an infinite sequence of flows on the solution space of the N=4 SYM equations. The dependence of the SYM fields on the parameters along the flows can be recovered by solving the equations of the hierarchy. We embed the N=4 SYM equations in the infinite system of the hierarchy equations and show that this SYM hierarchy is associated with an infinite set of graded symmetries recursively generated from supertranslations. Presumably, the existence of such nonlocal symmetries underlies the observed integrable structures in quantum N=4 SYM theory.Comment: 24 page

Sound scattering by several zooplankton groups. I. Experimental determination of dominant scattering mechanisms

Author Posting. © Acoustical Society of America, 1998. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 103 (1998): 225-235, doi:10.1121/1.421469.The acoustic scattering properties of live individual zooplankton from several gross anatomical groups have been investigated. The groups involve (1) euphausiids (Meganyctiphanes norvegica) whose bodies behave acoustically as a fluid material, (2) gastropods (Limacina retroversa) whose bodies include a hard elastic shell, and (3) siphonophores (Agalma okeni or elegans and Nanomia cara) whose bodies contain a gas inclusion (pneumatophore). The animals were collected from ocean waters off New England (Slope Water, Georges Bank, and the Gulf of Maine). The scattering properties were measured over parts or all of the frequency range 50 kHz to 1 MHz in a laboratory-style pulse-echo setup in a large tank at sea using live fresh specimens. Individual echoes as well as averages and ping-to-ping fluctuations of repeated echoes were studied. The material type of each group is shown to strongly affect both the overall echo level and pattern of the target strength versus frequency plots. In this first article of a two-part series, the dominant scattering mechanisms of the three animal types are determined principally by examining the structure of both the frequency spectra of individual broadband echoes and the compressed pulse (time series) output. Other information is also used involving the effect on overall levels due to (1) animal orientation and (2) tissue in animals having a gas inclusion (siphonophores). The results of this first paper show that (1) the euphausiids behave as weakly scattering fluid bodies and there are major contributions from at least two parts of the body to the echo (the number of contributions depends upon angle of orientation and shape), (2) the gastropods produce echoes from the front interface and possibly from a slow-traveling circumferential (Lamb) wave, and (3) the gas inclusion of the siphonophore dominates the echoes, but the tissue plays a role in the scattering and is especially important when analyzing echoes from individual animals on a ping-by-ping basis. The results of this paper serve as the basis for the development of acoustic scattering models in the companion paper [Stanton et al., J. Acoust. Soc. Am. 103, 236–253 (1998)].This work was supported by the National Science Foundation Grant No. OCE- 9201264, the U.S. Office of Naval Research Grant Nos. N00014-89-J-1729 and N00014-95-1-0287, and the MIT/ WHOI Joint Graduate Education Program

Contrasting demographic histories revealed in two invasive populations of the dry rot fungus Serpula lacrymans

Globalization and international trade have impacted organisms around the world leading to a considerable number of species establishing in new geographic areas. Many organisms have taken advantage of human-made environments, including buildings. One such species is the dry rot fungus Serpula lacrymans, which is the most aggressive wood-decay fungus in indoor environments in temperate regions. Using population genomic analyses of 36 full genome sequenced isolates, we demonstrated that European and Japanese isolates are highly divergent and the populations split 3000–19,000 generations ago, probably predating human influence. Approximately 250 generations ago, the European population went through a tight bottleneck, probably corresponding to the fungus colonization of the built environment in Europe. The demographic history of these populations, probably lead to low adaptive potential. Only two loci under selection were identified using a Fst outlier approach, and selective sweep analyses identified three loci with extended haplotype homozygosity. The selective sweep analyses found signals in genes possibly related to decay of various substrates in Japan and in genes involved DNA replication and protein modification in Europe. Our results suggest that the dry rot fungus independently established in indoor environments in Europe and Japan and that invasive species can potentially establish large populations in new habitats based on a few colonizing individuals