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Search Results: 1 - 10 of 302898 matches for " Susan J Clark "
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Epigenetic and phenotypic changes result from a continuous pre and post natal dietary exposure to phytoestrogens in an experimental population of mice
Carlos M Guerrero-Bosagna, Pablo Sabat, Fernanda S Valdovinos, Luis E Valladares, Susan J Clark
BMC Physiology , 2008, DOI: 10.1186/1472-6793-8-17
Abstract: Vaginal opening was advanced in female pups in the ISF group, from 31.6 ± 0.75 dpn to 25.7 ± 0.48. No differences in size or weight at ages 7, 14 or 21 dpn were detected between experimental groups. Nevertheless, at age 42 dpn reduced size and weight were observed in ISF pups, in addition to suppression of normal gender differences in weight seen in the control group (males heavier that females). Also, natural differences seen in DNA methylation at Acta1 promoter in the offspring originated in the control group were suppressed in the ISF group. Acta1 is known to be developmentally regulated and related to morphomotric features.This study demonstrates in mammals that individuals from a population subjected to a high consumption of isoflavones can show alterations in characters that may be of importance from an evolutionary perspective, such as epigenetic and morphometric characters or sexual maturation, a life history character.The evolutionary origin of new characters in a lineage is considered to be a process different from that of maintenance of these characters through generations [1,2]. Embryonic development plays an important role in the origin of viable phenotypic variation, on which natural selection may act further, thus, from an evolutionary perspective it is important to understand morphogenic processes taking place during early development [3]. Morphological transformations throughout evolutionary history have been produced from context-dependent changes in genetic processes that occur during development [4]. Considering the genome as responsive to environment has led to the hypothesis from us and others that development and/or epigenetics can provide sources of variation that are dependent on the environmental context [5-7]. Moreover epigenetic status in adulthood is directionally dependent on the animal's nutritional status during early development [8,9]. Nevertheless, few studies until recently have devoted attention to environmental compounds that cou
Using staffing ratios for workforce planning: evidence on nine allied health professions
Linda Cartmill, Tracy A Comans, Michele J Clark, Susan Ash, Lorraine Sheppard
Human Resources for Health , 2012, DOI: 10.1186/1478-4491-10-2
Abstract: A systematic literature search using relevant MeSH headings of business, medical and allied health databases and relevant grey literature for the period 2000-2008 was undertaken.Twelve articles were identified which described the use of workforce ratios in allied health services. Only one of these was a staffing ratio linked to clinical outcomes. The most comprehensive measures were identified in rehabilitation medicine.The evidence for use of staffing ratios for allied health practitioners is scarce and lags behind the fields of nursing and medicine.Health care worldwide is a large and expensive industry for which there are high consumer expectations. As health care increasingly relies on expensive technologies and drugs, governments are under mounting pressure to find ways to contain costs. Managing staff costs has emerged as a major area of focus [1,2]. It has become apparent that there are service over-laps [3,4], and that staff allocation must be evidence-based [5,6] and focused on the needs of the population serviced rather than continuing with traditional areas and modes of service [7-9]. The Australian Productivity Commission recently identified under-utilisation of the professional competencies of staff as an area of concern for the Australian health workforce [10].When introducing new services and reviewing current service delivery models, managers must make decisions on what constitutes appropriate levels of staffing. Different methods such as ratios; where staff are provided in a set ratio per measure such as bed numbers or population; and staffing according to patient acuity (for acute care services) are methods used in health care services for determining appropriate staff levels. While models of this type have been used successfully with nursing [11-13], and medical specialty professions [14], what constitutes appropriate levels of staffing for allied health professionals (AHPs) is less clear.An Australian study [15,16] reviewed a number of workload c
All-optical switching in rubidium vapor
Andrew M. C. Dawes,Lucas Illing,Susan M. Clark,Daniel J. Gauthier
Physics , 2005, DOI: 10.1126/science.1110151
Abstract: We report on an all-optical switch that operates at low light levels. It consists of laser beams counterpropagating through a warm rubidium vapor that induce an off-axis optical pattern. A switching laser beam causes this pattern to rotate even when the power in the switching beam is much lower than the power in the pattern. The observed switching energy density is very low, suggesting that the switch might operate at the single-photon level with system optimization. This approach opens the possibility of realizing a single-photon switch for quantum information networks and for improving transparent optical telecommunication networks.
Discovery pipeline for epigenetically deregulated miRNAs in cancer: integration of primary miRNA transcription
Toby Hulf, Tennille Sibbritt, Erik D Wiklund, Saul Bert, Dario Strbenac, Aaron L Statham, Mark D Robinson, Susan J Clark
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-54
Abstract: Using an integrative approach that combines primary transcription, genome-wide DNA methylation and H3K9Ac marks with microRNA (miRNA) expression, we identified miRNA genes that were epigenetically modified in cancer. We find miR-205, miR-21, and miR-196b to be epigenetically repressed, and miR-615 epigenetically activated in prostate cancer cells.We show that detecting changes in primary miRNA transcription levels is a valuable method for detection of local epigenetic modifications that are associated with changes in mature miRNA expression.MiRNA genes are typically transcribed by RNA polymerase II into primary miRNA (pri-miRNA) transcripts, and transcription appears to be regulated in a similar process as traditional coding genes [1]. Pri-miRNA transcripts are long non-coding RNAs (ncRNA) with stem-loop secondary structures that contain precursor miRNAs (pre-miRNA). Pri-miRNA transcripts are cleaved co-transcriptionally by the enzyme Drosha into stem loop pre-miRNAs, which are exported to the cytoplasm by Exportin 5, and further processed by Dicer into mature miRNA that can be loaded in the RNA induced silencing complex (RISC). Pre-miRNA levels are low relative to pri- and mature miRNAs, suggesting that dicing is an efficient mechanism with little regulation [2]. During development, many pri-miRNAs are expressed but not efficiently processed to mature miRNA [3]. In healthy tissues, the ratio of pri- to mature miRNAs has been shown to be close to one, while in cancer cells, a large number of miRNA genes are transcribed but not processed to mature miRNA [4]. An expanding body of evidence supports a role for miRNAs in disease progression and the potential for epigenetic mechanisms to regulate miRNA expression [5,6]. Epigenetics is the heritable modification of gene expression without changes in the DNA sequence. The importance of regulated epigenetic information is highlighted by the disruption of multiple epigenetic marks in various disease states, including cancer,
Impact of the Genome on the Epigenome Is Manifested in DNA Methylation Patterns of Imprinted Regions in Monozygotic and Dizygotic Twins
Marcel W. Coolen,Aaron L. Statham,Wenjia Qu,Megan J. Campbell,Anjali K. Henders,Grant W. Montgomery,Nick G. Martin,Susan J. Clark
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0025590
Abstract: One of the best studied read-outs of epigenetic change is the differential expression of imprinted genes, controlled by differential methylation of imprinted control regions (ICRs). To address the impact of genotype on the epigenome, we performed a detailed study in 128 pairs of monozygotic (MZ) and 128 pairs of dizygotic (DZ) twins, interrogating the DNA methylation status of the ICRs of IGF2, H19, KCNQ1, GNAS and the non-imprinted gene RUNX1. While we found a similar overall pattern of methylation between MZ and DZ twins, we also observed a high degree of variability in individual CpG methylation levels, notably at the H19/IGF2 loci. A degree of methylation plasticity independent of the genome sequence was observed, with both local and regional CpG methylation changes, discordant between MZ and DZ individual pairs. However, concordant gains or losses of methylation, within individual twin pairs were more common in MZ than DZ twin pairs, indicating that de novo and/or maintenance methylation is influenced by the underlying DNA sequence. Specifically, for the first time we showed that the rs10732516 [A] polymorphism, located in a critical CTCF binding site in the H19 ICR locus, is strongly associated with increased hypermethylation of specific CpG sites in the maternal H19 allele. Together, our results highlight the impact of the genome on the epigenome and demonstrate that while DNA methylation states are tightly maintained between genetically identical and related individuals, there remains considerable epigenetic variation that may contribute to disease susceptibility.
Performance Characteristics of the Cepheid Xpert MTB/RIF Test in a Tuberculosis Prevalence Survey
Susan E. Dorman,Violet N. Chihota,James J. Lewis,Maunank Shah,David Clark,Alison D. Grant,Gavin J. Churchyard,Katherine L. Fielding
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043307
Abstract: Xpert MTB/RIF (“Xpert”) is a molecular test for detection of Mycobacterium tuberculosis (MTB) in sputum. Performance characteristics have been established for its use during passive tuberculosis (TB) case detection in symptomatic TB suspects, but Xpert performance has not been assessed in other settings. Objectives were to determine Xpert performance and costs in the context of a TB prevalence survey.
"I Wish for More Than I Ever Get": Employers’ Perspectives on Employability Attributes of Architecture Graduates  [PDF]
Susan J. Shannon
Creative Education (CE) , 2012, DOI: 10.4236/ce.2012.326153
Abstract: This research considers graduate recruitment for architecture graduates. Employers in small, medium and large Australian firms, from the private and public sector were surveyed about their graduate hiring practices. Through distilling the discipline specific Graduate Attributes for all Australian Architecture Schools’ Architecture Programs, and generic Graduate Attributes for their Universities, the researcher compiled a questionnaire which was administered to prospective employers of architecture graduates. The results reveal that the possession of technical knowledge is more highly rated as a Graduate Attribute in recruitment than the possession of design knowledge/skills, and that the possession of Computer Aided Design (CAD) representation skills is more important to graduate recruiters of all firm sizes than either technical or design knowledge and skills. The research further revealed that the presentation of a portfolio is a key recruitment tool for employers, and that the demonstration of team work is a highly valued generic attribute for employers.
Permissive Transcriptional Activity at the Centromere through Pockets of DNA Hypomethylation
Nicholas C Wong,Lee H Wong,Julie M Quach,Paul Canham,Jeffrey M Craig,Jenny Z Song,Susan J Clark,K. H. Andy Choo
PLOS Genetics , 2006, DOI: 10.1371/journal.pgen.0020017
Abstract: DNA methylation is a hallmark of transcriptional silencing, yet transcription has been reported at the centromere. To address this apparent paradox, we employed a fully sequence-defined ectopic human centromere (or neocentromere) to investigate the relationship between DNA methylation and transcription. We used sodium bisulfite PCR and sequencing to determine the methylation status of 2,041 CpG dinucleotides distributed across a 6.76-Mbp chromosomal region containing a neocentromere. These CpG dinucleotides were associated with conventional and nonconventional CpG islands. We found an overall hypermethylation of the neocentric DNA at nonconventional CpG islands that we designated as CpG islets and CpG orphans. The observed hypermethylation was consistent with the presence of a presumed transcriptionally silent chromatin state at the neocentromere. Within this neocentric chromatin, specific sites of active transcription and the centromeric chromatin boundary are defined by DNA hypomethylation. Our data demonstrate, for the first time to our knowledge, a correlation between DNA methylation and centromere formation in mammals, and that transcription and “chromatin-boundary activity” are permissible at the centromere through the selective hypomethylation of pockets of sequences without compromising the overall silent chromatin state and function of the centromere.
Role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein D
Kevan L Hartshorn, Richard Webby, Mitchell R White, Tesfaldet Tecle, Clark Pan, Susan Boucher, Rodney J Moreland, Erika C Crouch, Ronald K Scheule
Respiratory Research , 2008, DOI: 10.1186/1465-9921-9-65
Abstract: We tested antiviral activities of recombinant human SP-D against a panel of IAV strains that vary in glycosylation sites on their hemagglutinin (HA). For these experiments a recombinant version of human SP-D of the Met11, Ala160 genotype was used after it was characterized biochemically and structurally.Oligosaccharides at amino acid 165 on the HA in the H3N2 subtype and 104 in the H1N1 subtype are absent in collectin-resistant strains developed in vitro and are important for mediating antiviral activity of SP-D; however, other glycans on the HA of these viral subtypes also are involved in inhibition by SP-D. H3N2 strains obtained shortly after introduction into the human population were largely resistant to SP-D, despite having the glycan at 165. H3N2 strains have become steadily more sensitive to SP-D over time in the human population, in association with addition of other glycans to the head region of the HA. In contrast, H1N1 strains were most sensitive in the 1970s–1980s and more recent strains have become less sensitive, despite retaining the glycan at 104. Two H5N1 strains were also resistant to inhibition by SP-D. By comparing sites of glycan attachment on sensitive vs. resistant strains, specific glycan sites on the head domain of the HA are implicated as important for inhibition by SP-D. Molecular modeling of the glycan attachment sites on HA and the carbohydrate recognition domain of SPD are consistent with these observations.Inhibition by SP-D correlates with presence of several glycan attachment sites on the HA. Pandemic and avian strains appear to lack susceptibility to SP-D and this could be a contributory factor to their virulence.Influenza A viruses (IAVs) remain a major cause of morbidity and mortality and have the potential to cause massive mortality if novel pandemic strains emerge through reassortment of human and avian strains or direct adaptation of avian strains to humans (as appears to have occurred in 1918) [1,2]. Certain groups of subjects
BayMeth: Improved DNA methylation quantification for affinity capture sequencing data using a flexible Bayesian approach
Andrea Riebler,Mirco Menigatti,Jenny Z. Song,Aaron L. Statham,Clare Stirzaker,Nadiya Mahmud,Charles A. Mein,Susan J. Clark,Mark D. Robinson
Quantitative Biology , 2013,
Abstract: DNA methylation (DNAme) is a critical component of the epigenetic regulatory machinery and aberrations in DNAme patterns occur in many diseases, such as cancer. Mapping and understanding DNAme profiles offers considerable promise for reversing the aberrant states. There are several approaches to analyze DNAme, which vary widely in cost, resolution and coverage. Affinity capture and high-throughput sequencing of methylated DNA strike a good balance between the high cost of whole genome bisulphite sequencing (WGBS) and the low coverage of methylation arrays. However, existing methods cannot adequately differentiate between hypomethylation patterns and low capture efficiency, and do not offer flexibility to integrate copy number variation (CNV). Furthermore, no uncertainty estimates are provided, which may prove useful for combining data from multiple protocols or propagating into downstream analysis. We propose an empirical Bayes framework that uses a fully methylated (i.e. SssI treated) control sample to transform observed read densities into regional methylation estimates. In our model, inefficient capture can be distinguished from low methylation levels by means of larger posterior variances. Furthermore, we can integrate CNV by introducing a multiplicative offset into our Poisson model framework. Notably, our model offers analytic expressions for the mean and variance of the methylation level and thus is fast to compute. Our algorithm outperforms existing approaches in terms of bias, mean-squared error and coverage probabilities as illustrated on multiple reference datasets. Although our method provides advantages even without the SssI-control, considerable improvement is achieved by its incorporation. Our method can be applied to methylated DNA affinity enrichment assays (e.g MBD-seq, MeDIP-seq) and a software implementation is available in the Bioconductor Repitools package.
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