22 results on '"Melinda Power"'
Search Results
2. Life’s Simple 7 and the Risk of Dementia among Women (P2-5.030)
- Author
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Pamela Rist, Melinda Power, I-Min Lee, and Julie Buring
- Published
- 2023
3. Abstract TMP101: Post-stroke Cognitive Impairment And The Risk Of Recurrent Stroke And Death: Systematic Review And Meta-analysis
- Author
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N. Maritza Dowling, Skylar Johnson, Melinda Power, and Zurab Nadareishvili
- Subjects
Advanced and Specialized Nursing ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Post-stroke cognitive impairment (PSCI) occurs in 20-40% of patients 3-6 months after stroke. However, the question regarding risks of recurrent stroke and death in patients with PSCI remains controversial. The goal of this study was to conduct meta-analysis of published literature to estimate the risks of stroke recurrence and death associated with PSCI, as well as to assess the quality of these studies, and to identify sources of variation. Electronic databases (PubMed, EMbase, Google Scholar, Cochrane Library, and Scopus) were screened for eligible studies published from 1992 to 2019. Study quality was assessed using the Newcastle Ottawa Scale. Risk of bias in non-randomized and randomized studies was assessed using ROBINS-E and RoB 2 tools, respectively. Funnel plots and selection models were used for evaluating publication bias. Heterogeneity was assessed using a combination of statistics: I 2 , Q -statistic, and Kendall τ 2 . Estimates were obtained using a random effects model and restricted maximum likelihood estimation. Pooled estimates for the two outcomes of interest were calculated as hazard ratios (HR) with 95% confidence intervals (CIs). We included eight studies examining the effect of PSCI on risk of stroke recurrence. We found no evidence of potential publication bias among the included studies in stroke recurrence (χ 2 =3.440, p=0.487) and mortality (χ 2 =3.797, p=0.150). Pooled data from the eight studies involving n=1,840 PSCI and n=5,824 non-PSCI showed that the hazard of recurrent stroke risk was significantly higher in individuals with PSCI compared to non-PSCI participants (HR = 1.71; 95% CI: 1.45 - 2.01; I 2 = 0%). Seventeen studies were included examining the impact of PSCI on mortality risk. The pooled data from these studies comprised n=7,591 PSCI and n=22,328 non-PSCI study participants. The pooled hazard of mortality was significantly higher in the PSCI group relative to the non-PSCI group (HR = 1.98; 95% CI: 1.64 - 2.40; I 2 = 82.95%). This meta-analysis shows an increased risk of mortality and recurrent stroke in patients with PSCI. Post-stroke cognitive testing may identify patients at a higher risk of stroke recurrence and death who may require more aggressive interventions for secondary prevention.
- Published
- 2023
4. The association between long-term PM2.5 exposure and late-life amyloid burden in the Atherosclerosis Risk in Communities (ARIC) study cohort
- Author
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Erin Bennett, Xiaohui Xu, Katie Lynch, Eun Sug Park, Qi Ying, Richard Smith, James Stewart, Eric Whitsel, Thomas Mosley, Jeff Yanosky, Dean Wong, Duanping Liao, Rebecca Gottesman, and Melinda Power
- Subjects
General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
5. Comparison of PM2.5 air pollution exposure estimates at WHIMS participant locations based on different modelling approaches and impact on health effects estimation
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Melinda Power, Erin E. Bennett, Katie M. Lynch, James D. Stewart, Xiaohui Xu, Eun Sug Park, Qi Ying, Richard Smith, William Vizuete, Helene G. Margolis, Ramon Casanova, Robert Wallace, Lianne Sheppard, Marc Serre, Adam Szpiro, Jiu-Chiuan Chen, Jeff Yanosky, Duanping Liao, Gregory Wellenius, Joel Kaufman, and Eric Whitsel
- Subjects
General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
6. Comparison of PM2.5 concentrations estimated using eleven different methods and their associations with cognitive outcomes in the ARIC cohort
- Author
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Melinda Power, Katie Lynch, Erin Bennett, Qi Ying, Eun Sug Park, Xiaohui Xu, Richard Smith, James Stewart, Jeff Yanosky, Duanping Liao, Lianne Sheppard, Adam Spziro, and Eric Whitsel
- Subjects
General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
7. Association of residential road proximity with cognitive decline and dementia: The Atherosclerosis Risk in Communities (ARIC) Study
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Naa Adoley Parker-Allotey, Erin E. Bennett, Katie Lynch, Xiaohui Xu, Eric A. Whitsel, Richard L. Smith, James D. Stewart, Eun Sug Park, Qi Ying, and Melinda Power
- Subjects
General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
8. Challenges in Resource Utilization for Caregivers of Persons With Dementia: A qualitative Study
- Author
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Robert Turner, Jen Weaver, Eric Owens, Meredith Boe, Jessica Bride, Maritza Dowling, Christina Prather, and Melinda Power
- Subjects
Abstracts ,Health (social science) ,Session 4605 (Symposium) ,Life-span and Life-course Studies ,AcademicSubjects/SOC02600 ,Health Professions (miscellaneous) - Abstract
This study highlights primary caregivers’ experiences with health department policies designed to support people with cognitive impairment/Alzheimer’s Disease and Related Dementias (ADRD). Caregivers were defined as individuals aged 45-85 that provide at least 10 hours of unpaid care. Five, 90-minute focus groups were conducted virtually with 24 caregivers of individuals with cognitive impairment/ADRD. Transcripts were analyzed thematically. Caregivers were primarily Black females (75%) with at least a high school education (42%). Care recipients were likely to be community-dwelling parents (71%), with moderate or advanced (79%) dementia. Caregivers described challenges with accessing resources intended for care recipients, especially as cognitive impairment worsened. Caregivers reported providing care 24/7 as traumatizing. Home-based personal aides and companionship services did not reduce this burden. COVID-19 impacted caregivers and care recipient’s access to resources increasing burden. Policies need to be flexible for ever-changing needs of individuals with ADRD and support the overall well-being of the caregivers.
- Published
- 2021
9. Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix interactions and mesenchyme maintenance
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Junwen Wang, Vanessa Jones, Melinda Power, Heidi Bildsoe, Xiaochen Fan, Patrick P.L. Tam, David A.F. Loebel, Emilie E. Wilkie, Jing Qin, and Ator Ashoti
- Subjects
0301 basic medicine ,PROTEIN ,FGF and mesoderm formation ,Madin Darby Canine Kidney Cells ,bHLH factor ,Mesoderm ,Mice ,Craniofacial ,Cranial mesoderm ,Genetics ,Mice, Knockout ,CRANIOFACIAL MUSCLES ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,Cell Differentiation ,TGF-BETA ,Cell biology ,Extracellular Matrix ,DOMAIN RECEPTOR 2 ,medicine.anatomical_structure ,DIFFERENTIATION ,Neural Crest ,embryonic structures ,NEURAL-TUBE ,Twist1 ,PROMOTES TUMOR-METASTASIS ,Epithelial-Mesenchymal Transition ,animal structures ,Mesenchyme ,Morphogenesis ,Biology ,Cell Line ,03 medical and health sciences ,Dogs ,TGF beta signaling pathway ,medicine ,Paraxial mesoderm ,Animals ,BREAST-CANCER ,Molecular Biology ,Binding Sites ,BETA-IG-H3 INTERACTS ,Skull ,Twist-Related Protein 1 ,Mesenchymal Stem Cells ,Cell Biology ,030104 developmental biology ,Extracellular matrix-cell interaction ,MORPHOGENESIS ,NODAL ,Developmental Biology ,TGFBI - Abstract
TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. We have previously shown that, in the absence of TWIST1, cells within the cranial mesoderm adopt an abnormal epithelial configuration via a process reminiscent of a mesenchymal to epithelial transition (MET). Here, we show by gene expression analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. ChIP-seq was used to identify TWIST1-binding sites in an in vitro model of a TWIST1-dependent mesenchymal cell state, and the data were combined with the transcriptome data to identify potential target genes. Three direct transcriptional targets of TWIST1 (Ddr2, Pcolce and Tgfbi) were validated by ChIP-PCR using mouse embryonic tissues and by luciferase assays. Our findings reveal that the mesenchymal properties of the cranial mesoderm are likely to be regulated by a network of TWIST1 targets that influences the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures.
- Published
- 2016
10. Abstract P020: Atrial Fibrillation and White Matter Microstructural Integrity: The Atherosclerosis Risk in Communities Neurocognitive Study
- Author
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Iris Yuefan Shao, Melinda Power, Thomas Mosley, Rebecca Gottesman, Lin Chen, Faye Norby, Elsayed Soliman, and Alvaro Alonso
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Evidence suggests atrial fibrillation (AF) is associated with increased risk of cognitive decline and dementia, even in the absence of stroke. Pathways such as AF-induced brain hypoperfusion and small vessel disease resulting in white matter abnormalities may also compromise cerebrovasculature and brain tissue, which would lead to cognitive impairment and dementia. However, mechanisms responsible for the association between AF and cognitive impairment independent of stroke and cerebral infarcts remain relatively unexplored. The study aims to assess the cross-sectional association between prevalent AF and white matter microstructural integrity (WMMI) as a marker for cerebrovascular disease. Methods: We performed a cross-sectional analysis of 1937 participants attending the ARIC-Neurocognitive Study (ARIC-NCS) in 2011-2013 that were either black or white and with brain magnetic resonance imaging (MRI). Prevalent AF was defined by a history of AF based on study ECG and hospitalization record. WMMI was defined using regional average fractional anisotropy and mean diffusivity from Diffusion Tensor Imaging measurements in the MRI. We excluded participants with a prior history of stroke or cerebral infarct. A multivariable regression model was used to assess the association between AF and WMMI measures. Results: Among 1943 participants (mean age = 76 years, 28% black, 60% female), 7% (N= 133) had prevalent AF. After multivariable adjustment, prevalence of AF was not associated with WMMI measurements (Table). Conclusion: In a community-based study, prevalent AF was not independently associated with WMMI in the absence of stroke or cerebral infarct. However, the reduced sample size of the AF population as well as the cross-sectional study design are important limitations. Further longitudinal studies are needed to investigate prospectively the association of AF with early markers of white matter disease.
- Published
- 2018
11. Is cell culture a risky business? Risk analysis based on scientist survey data
- Author
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Lily I. Huschtscha, Melinda Power, Jonathan W. Arthur, Mark Shannon, Elsa L. Moy, Elaine Eggington, Roger R. Reddel, Amanda Capes-Davis, and Ronnie Georghiou
- Subjects
0301 basic medicine ,Cancer Research ,business.industry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Tissue bank ,Survey data collection ,Medicine ,Marketing ,Risk assessment ,business - Abstract
Cell culture is a technique that requires vigilance from the researcher. Common cell culture problems, including contamination with microorganisms or cells from other cultures, can place the reliability and reproducibility of cell culture work at risk. Here we use survey data, contributed by research scientists based in Australia and New Zealand, to assess common cell culture risks and how these risks are managed in practice. Respondents show that sharing of cell lines between laboratories continues to be widespread. Arrangements for mycoplasma and authentication testing are increasingly in place, although scientists are often uncertain how to perform authentication testing. Additional risks are identified for preparation of frozen stocks, storage and shipping.
- Published
- 2015
12. C to U <scp>RNA</scp> editing mediated by <scp>APOBEC</scp> 1 requires <scp>RNA</scp> ‐binding protein <scp>RBM</scp> 47
- Author
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David A.F. Loebel, Kristen Barratt, Vanessa Jones, Doreen Liebhold, Nicolas Fossat, Tania Radziewic, Melinda Power, Patrick P.L. Tam, Karin Tourle, and Joshua B. Studdert
- Subjects
Apolipoprotein B ,APOBEC-1 Deaminase ,Gene Expression ,Mice, Transgenic ,RNA-binding protein ,Cytidine ,Biochemistry ,chemistry.chemical_compound ,Cytidine Deaminase ,Gene expression ,Genetics ,Animals ,Humans ,RNA, Messenger ,Uridine ,Molecular Biology ,Cell Nucleus ,biology ,APOBEC1 ,Scientific Reports ,RNA-Binding Proteins ,Cytidine deaminase ,Molecular biology ,Cell biology ,Protein Transport ,chemistry ,RNA editing ,biology.protein ,RNA Editing ,Caco-2 Cells - Abstract
Cytidine (C) to Uridine (U) RNA editing is a post-transcriptional modification that is accomplished by the deaminase APOBEC1 and its partnership with the RNA-binding protein A1CF. We identify and characterise here a novel RNA-binding protein, RBM47, that interacts with APOBEC1 and A1CF and is expressed in tissues where C to U RNA editing occurs. RBM47 can substitute for A1CF and is necessary and sufficient for APOBEC1-mediated editing in vitro. Editing is further impaired in Rbm47-deficient mutant mice. These findings suggest that RBM47 and APOBEC1 constitute the basic machinery for C to U RNA editing.
- Published
- 2014
13. The Transcriptional and Functional Properties of Mouse Epiblast Stem Cells Resemble the Anterior Primitive Streak
- Author
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Vanessa Jones, Melinda Power, Joshua B. Studdert, Angelyn Hor, Kirsten A. Steiner, Yoji Kojima, David A.F. Loebel, Patrick P.L. Tam, Oliver H. Tam, Grant J Logan, Erdahl Teber, Keren Kaufman-Francis, Hilda A. Pickett, Gustavo de Alencastro, Michael D. Stutz, and Ian E. Alexander
- Subjects
Pluripotent Stem Cells ,animal structures ,Primitive Streak ,Cellular differentiation ,Blotting, Western ,Ectoderm ,Biology ,Real-Time Polymerase Chain Reaction ,Immunoenzyme Techniques ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Animals ,Cell Lineage ,RNA, Messenger ,Induced pluripotent stem cell ,Cells, Cultured ,Embryonic Stem Cells ,Cell Proliferation ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,0303 health sciences ,Reverse Transcriptase Polymerase Chain Reaction ,Primitive streak ,Gene Expression Profiling ,Gastrulation ,Cell Differentiation ,Cell Biology ,Fibroblasts ,Embryo, Mammalian ,Embryonic stem cell ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Epiblast ,embryonic structures ,Molecular Medicine ,Female ,Stem cell ,Biomarkers ,Germ Layers ,030217 neurology & neurosurgery - Abstract
SummaryMouse epiblast stem cells (EpiSCs) can be derived from a wide range of developmental stages. To characterize and compare EpiSCs with different origins, we derived a series of EpiSC lines from pregastrula stage to late-bud-stage mouse embryos. We found that the transcriptomes of these cells are hierarchically distinct from those of the embryonic stem cells, induced pluripotent stem cells (iPSCs), and epiblast/ectoderm. The EpiSCs display globally similar gene expression profiles irrespective of the original developmental stage of the source tissue. They are developmentally similar to the ectoderm of the late-gastrula-stage embryo and behave like anterior primitive streak cells when differentiated in vitro and in vivo. The EpiSC lines that we derived can also be categorized based on a correlation between gene expression signature and predisposition to differentiate into particular germ-layer derivatives. Our findings therefore highlight distinct identifying characteristics of EpiSCs and provide a foundation for further examination of EpiSC properties and potential.
- Published
- 2014
14. Generation of Mice Deficient in both KLF3/BKLF and KLF8 Reveals a Genetic Interaction and a Role for These Factors in Embryonic Globin Gene Silencing
- Author
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Melinda Power, Alister P. W. Funnell, Ka Sin Mak, Andrew C. Perkins, Natalie A. Twine, Laura J. Norton, Patrick P.L. Tam, Stuart T. Fraser, Tania Radziewic, Richard C. M. Pearson, Marc R. Wilkins, Gregory J. Pelka, Kim S. Bell-Anderson, and Merlin Crossley
- Subjects
Male ,Mutant ,Kruppel-Like Transcription Factors ,KLF1 ,Biology ,Mice ,Chlorocebus aethiops ,Gene expression ,Animals ,Gene silencing ,Gene Silencing ,Globin ,Molecular Biology ,Transcription factor ,Gene ,Genetics ,Gene Expression Regulation, Developmental ,Articles ,Cell Biology ,Globins ,Mice, Inbred C57BL ,Liver ,COS Cells ,KLF3 ,Female ,Transcription Factors - Abstract
Krüppel-like factors 3 and 8 (KLF3 and KLF8) are highly related transcriptional regulators that bind to similar sequences of DNA. We have previously shown that in erythroid cells there is a regulatory hierarchy within the KLF family, whereby KLF1 drives the expression of both the Klf3 and Klf8 genes and KLF3 in turn represses Klf8 expression. While the erythroid roles of KLF1 and KLF3 have been explored, the contribution of KLF8 to this regulatory network has been unknown. To investigate this, we have generated a mouse model with disrupted KLF8 expression. While these mice are viable, albeit with a reduced life span, mice lacking both KLF3 and KLF8 die at around embryonic day 14.5 (E14.5), indicative of a genetic interaction between these two factors. In the fetal liver, Klf3 Klf8 double mutant embryos exhibit greater dysregulation of gene expression than either of the two single mutants. In particular, we observe derepression of embryonic, but not adult, globin expression. Taken together, these results suggest that KLF3 and KLF8 have overlapping roles in vivo and participate in the silencing of embryonic globin expression during development.
- Published
- 2013
15. Rhou maintains the epithelial architecture and facilitates differentiation of the foregut endoderm
- Author
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David A.F. Loebel, Vanessa Jones, Melinda Power, Kirsten A. Steiner, Lorraine Robb, Leigh Coultas, Renuka S. Rao, Nicolas Fossat, Patrick P.L. Tam, Yvette Jackson, Joshua B. Studdert, and Tania Radziewic
- Subjects
rho GTP-Binding Proteins ,animal structures ,organogenesis ,Cellular differentiation ,Morphogenesis ,embryo ,Embryoid body ,Biology ,Cell Line ,Mice ,medicine ,Animals ,Humans ,polarity ,RNA, Small Interfering ,endoderm ,Molecular Biology ,Embryonic Stem Cells ,Mice, Knockout ,Base Sequence ,Gene Expression Regulation, Developmental ,Cell Differentiation ,cytoskeleton ,Foregut ,Hep G2 Cells ,differentiation ,Anatomy ,Embryonic stem cell ,Actins ,Cell biology ,Wnt Proteins ,Intercellular Junctions ,medicine.anatomical_structure ,Gene Knockdown Techniques ,embryonic structures ,NIH 3T3 Cells ,Commentary ,Endoderm ,epithelium ,Digestive System ,Developmental biology ,Signal Transduction ,Developmental Biology ,Definitive endoderm - Abstract
Rhou encodes a Cdc42-related atypical Rho GTPase that influences actin organization in cultured cells. In mouse embryos at early-somite to early-organogenesis stages, Rhou is expressed in the columnar endoderm epithelium lining the lateral and ventral wall of the anterior intestinal portal. During foregut development, Rhou is downregulated in regions where the epithelium acquires a multilayered morphology heralding the budding of organ primordia. In embryos generated from Rhou knockdown embryonic stem (ES) cells, the embryonic foregut displays an abnormally flattened shape. The epithelial architecture of the endoderm is disrupted, the cells are depleted of microvilli and the phalloidin-stained F-actin content of their sub-apical cortical domain is reduced. Rhou-deficient cells in ES cell-derived embryos and embryoid bodies are less efficient in endoderm differentiation. Impaired endoderm differentiation of Rhou-deficient ES cells is accompanied by reduced expression of c-Jun/AP-1 target genes, consistent with a role for Rhou in regulating JNK activity. Downregulation of Rhou in individual endoderm cells results in a reduced ability of these cells to occupy the apical territory of the epithelium. Our findings highlight epithelial morphogenesis as a required intermediate step in the differentiation of endoderm progenitors. In vivo, Rhou activity maintains the epithelial architecture of the endoderm progenitors, and its downregulation accompanies the transition of the columnar epithelium in the embryonic foregut to a multilayered cell sheet during organ formation.
- Published
- 2011
16. Sox17-dependent gene expression and early heart and gut development in Sox17-deficient mouse embryos
- Author
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Germaine L. Truisi, Patrick P.L. Tam, Kirsten A. Steiner, Yoshiakira Kanai, David A.F. Loebel, Melinda Power, Vanessa Jones, Masami Kanai-Azuma, Poh-Lynn Khoo, and Sabine Pfister
- Subjects
Male ,Embryology ,Heart morphogenesis ,Mice, 129 Strain ,animal structures ,Cell Transplantation ,Green Fluorescent Proteins ,Mutant ,Mice, Transgenic ,Biology ,Mice ,HMGB Proteins ,Gene expression ,SOXF Transcription Factors ,Animals ,Humans ,Progenitor cell ,Gene ,In Situ Hybridization ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,Genetics ,Heart development ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Myocardium ,Endoderm ,Gene Expression Regulation, Developmental ,Heart ,Hep G2 Cells ,Embryo, Mammalian ,Cell biology ,Gastrointestinal Tract ,Gene expression profiling ,Somites ,embryonic structures ,Female ,Developmental Biology ,Definitive endoderm - Abstract
Sox17 is a transcription factor that is required for maintenance of the definitive endoderm in mouse embryos. By expression profiling of wild-type and mutant embryos and Sox17-overexpressing hepatoma cells, we identified genes with Sox17-dependent expression. Among the genes that were up-regulated in Sox17-null embryos and down-regulated by Sox17 expressing HepG2 cells is a set of genes that are expressed in the developing liver, suggesting that one function of Sox17 is the repression of liver gene expression, which is compatible with a role for Sox17 in maintaining the definitive endoderm in a progenitor state. Consistent with these findings, Sox17(-/-) cells display a diminished capacity to contribute to the definitive endoderm when transplanted into wild-type hosts. Analysis of gene ontology further revealed that many genes related to heart development were downregulated in Sox17-null embryos. This is associated with the defective development of the heart in the mutant embryos, which is accompanied by localised loss of Myocd-expressing cardiogenic progenitors and the malformation of the anterior intestinal portal.
- Published
- 2011
17. Is cell culture a risky business? Risk analysis based on scientist survey data
- Author
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Mark, Shannon, Amanda, Capes-Davis, Elaine, Eggington, Ronnie, Georghiou, Lily I, Huschtscha, Elsa, Moy, Melinda, Power, Roger R, Reddel, and Jonathan W, Arthur
- Subjects
Laboratory Personnel ,Mycoplasma ,Biometric Identification ,Surveys and Questionnaires ,Cell Culture Techniques ,Humans ,Tissue Banks ,Risk Assessment - Abstract
Cell culture is a technique that requires vigilance from the researcher. Common cell culture problems, including contamination with microorganisms or cells from other cultures, can place the reliability and reproducibility of cell culture work at risk. Here we use survey data, contributed by research scientists based in Australia and New Zealand, to assess common cell culture risks and how these risks are managed in practice. Respondents show that sharing of cell lines between laboratories continues to be widespread. Arrangements for mycoplasma and authentication testing are increasingly in place, although scientists are often uncertain how to perform authentication testing. Additional risks are identified for preparation of frozen stocks, storage and shipping.
- Published
- 2015
18. Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo
- Author
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Chi Kin Ip, Richard R. Behringer, Patrick P.L. Tam, Karin Tourle, David A.F. Loebel, Nicolas Fossat, Kin Ming Kwan, Joshua B. Studdert, Poh Lynn Khoo, Melinda Power, Vanessa Jones, and Samara L. Lewis
- Subjects
Mesoderm ,animal structures ,LIM-Homeodomain Proteins ,Protocadherin ,Biology ,Models, Biological ,Transcription (biology) ,medicine ,Animals ,Molecular Biology ,Transcription factor ,Mice, Knockout ,Neuroectoderm ,Primitive streak ,Endoderm ,Wnt signaling pathway ,Gene Expression Regulation, Developmental ,Cadherins ,Embryo, Mammalian ,Cell biology ,Wnt Proteins ,medicine.anatomical_structure ,Phenotype ,DKK1 ,embryonic structures ,Mutation ,Cancer research ,Head ,Gene Deletion ,Germ Layers ,Developmental Biology ,Signal Transduction ,Transcription Factors - Abstract
Lhx1 encodes a LIM homeobox transcription factor that is expressed in the primitive streak, mesoderm and anterior mesendoderm of the mouse embryo. Using a conditional Lhx1 flox mutation and three different Cre deleters, we demonstrated that LHX1 is required in the anterior mesendoderm, but not in the mesoderm, for formation of the head. LHX1 enables the morphogenetic movement of cells that accompanies the formation of the anterior mesendoderm, in part through regulation of Pcdh7 expression. LHX1 also regulates, in the anterior mesendoderm, the transcription of genes encoding negative regulators of WNT signalling, such as Dkk1, Hesx1, Cer1 and Gsc. Embryos carrying mutations in Pcdh7, generated using CRISPR-Cas9 technology, and embryos without Lhx1 function specifically in the anterior mesendoderm displayed head defects that partially phenocopied the truncation defects of Lhx1-null mutants. Therefore, disruption of Lhx1-dependent movement of the anterior mesendoderm cells and failure to modulate WNT signalling both resulted in the truncation of head structures. Compound mutants of Lhx1, Dkk1 and Ctnnb1 show an enhanced head truncation phenotype, pointing to a functional link between LHX1 transcriptional activity and the regulation of WNT signalling. Collectively, these results provide comprehensive insight into the context-specific function of LHX1 in head formation: LHX1 enables the formation of the anterior mesendoderm that is instrumental for mediating the inductive interaction with the anterior neuroectoderm and LHX1 also regulates the expression of factors in the signalling cascade that modulate the level of WNT activity.
- Published
- 2014
19. Generation of mouse embryos with small hairpin RNA-mediated knockdown of gene expression
- Author
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David A F, Loebel, Tania, Radziewic, Melinda, Power, Joshua B, Studdert, and Patrick P L, Tam
- Subjects
Tetraploidy ,Blastomeres ,Mice ,Gene Knockdown Techniques ,Gene Targeting ,Animals ,Gene Expression Regulation, Developmental ,RNA, Small Interfering ,Embryo, Mammalian ,Molecular Biology ,Embryonic Stem Cells - Abstract
We are using knockdown of gene expression in mouse embryos by constitutive expression of small hairpin (sh)RNAs as a means of observing loss-of-function phenotypes more rapidly than gene targeting. Plasmid constructs that direct shRNA expression via an RNA pol III promoter are introduced into embryonic stem (ES) cells by electroporation and drug selection. Clones are propagated and the degree of knockdown assessed by quantitative protein or RNA methods. Selected ES cell clones are used to generate embryos by tetraploid complementation. Blastomeres of two cell embryos are electrofused to generate tetraploid embryos. Chimeric embryos are produced by injection of ES cells into blastocysts or aggregation with morulae. In these embryos, the tetraploid cells become excluded from the fetal tissues, resulting in ES cell-derived embryos harboring the shRNA knockdown construct. Embryos can be collected and their phenotype assessed by appropriate means.
- Published
- 2013
20. Generation of Mouse Embryos with Small Hairpin RNA-Mediated Knockdown of Gene Expression
- Author
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Tania Radziewic, David A.F. Loebel, Patrick P.L. Tam, Joshua B. Studdert, and Melinda Power
- Subjects
Small hairpin RNA ,Regulation of gene expression ,Gene knockdown ,animal structures ,Tetraploid complementation assay ,embryonic structures ,Gene expression ,Gene Knockdown Techniques ,Gene targeting ,RNA ,Biology ,Cell biology - Abstract
We are using knockdown of gene expression in mouse embryos by constitutive expression of small hairpin (sh)RNAs as a means of observing loss-of-function phenotypes more rapidly than gene targeting. Plasmid constructs that direct shRNA expression via an RNA pol III promoter are introduced into embryonic stem (ES) cells by electroporation and drug selection. Clones are propagated and the degree of knockdown assessed by quantitative protein or RNA methods. Selected ES cell clones are used to generate embryos by tetraploid complementation. Blastomeres of two cell embryos are electrofused to generate tetraploid embryos. Chimeric embryos are produced by injection of ES cells into blastocysts or aggregation with morulae. In these embryos, the tetraploid cells become excluded from the fetal tissues, resulting in ES cell-derived embryos harboring the shRNA knockdown construct. Embryos can be collected and their phenotype assessed by appropriate means.
- Published
- 2013
21. Differential response of epiblast stem cells to Nodal and Activin signalling: a paradigm of early endoderm development in the embryo
- Author
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Yoji Kojima, Hwee Ngee Goh, Melinda Power, Keren Kaufman-Francis, Emilie E. Wilkie, Vanessa Jones, Patrick P.L. Tam, Joshua B. Studdert, David A.F. Loebel, and Erdahl Teber
- Subjects
animal structures ,Nodal Protein ,Nodal signaling ,Embryoid body ,Germ layer ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Directed differentiation ,Transforming Growth Factor beta ,medicine ,Animals ,Embryonic Stem Cells ,Inhibin-beta Subunits ,Homeodomain Proteins ,Endoderm ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Articles ,Cell biology ,medicine.anatomical_structure ,Epiblast ,embryonic structures ,Immunology ,General Agricultural and Biological Sciences ,NODAL ,Germ Layers ,Signal Transduction ,Definitive endoderm - Abstract
Mouse epiblast stem cells (EpiSCs) display temporal differences in the upregulation ofMixl1expression during the initial steps ofin vitrodifferentiation, which can be correlated with their propensity for endoderm differentiation. EpiSCs that upregulatedMixl1rapidly during differentiation responded robustly to both Activin A and Nodal in generating foregut endoderm and precursors of pancreatic and hepatic tissues. By contrast, EpiSCs that delayed Mixl1 upregulation responded less effectively to Nodal and showed an overall suboptimal outcome of directed differentiation. The enhancement in endoderm potency in Mixl1-early cells may be accounted for by a rapid exit from the progenitor state and the efficient response to the induction of differentiation by Nodal. EpiSCs that readily differentiate into the endoderm cells are marked by a distinctive expression fingerprint of transforming growth factor (TGF)-β signalling pathway genes and genes related to the endoderm lineage. Nodal appears to elicit responses that are associated with transition to a mesenchymal phenotype, whereas Activin A promotes gene expression associated with maintenance of an epithelial phenotype. We postulate that the formation of definitive endoderm (DE) in embryoid bodies follows a similar process to germ layer formation from the epiblast, requiring an initial de-epithelialization event and subsequent re-epithelialization. Our results show that priming EpiSCs with the appropriate form of TGF-β signalling at the formative phase of endoderm differentiation impacts on the further progression into mature DE-derived lineages, and that this is influenced by the initial characteristics of the cell population. Our study also highlights that Activin A, which is commonly used as anin vitrosurrogate for Nodal in differentiation protocols, does not elicit the same downstream effects as Nodal, and therefore may not effectively mimic events that take place in the mouse embryo.
- Published
- 2014
22. Dataset of TWIST1-regulated genes in the cranial mesoderm and a transcriptome comparison of cranial mesoderm and cranial neural crest
- Author
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Heidi Bildsoe, Jing Qin, Vanessa Jones, Xiaochen Fan, Melinda Power, Patrick P.L. Tam, Junwen Wang, David A.F. Loebel, Emilie E. Wilkie, and Ator Ashoti
- Subjects
0301 basic medicine ,Mesoderm ,Multidisciplinary ,animal structures ,Mesenchyme ,Embryo ,Anatomy ,Biology ,lcsh:Computer applications to medicine. Medical informatics ,Chromatin ,Cell biology ,Transcriptome ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Cranial neural crest ,embryonic structures ,medicine ,Paraxial mesoderm ,lcsh:R858-859.7 ,lcsh:Science (General) ,NODAL ,Data Article ,lcsh:Q1-390 - Abstract
This article contains data related to the research article entitled “Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix interactions and mesenchyme maintenance” by Bildsoe et al. (2016) [1]. The data presented here are derived from: (1) a microarray-based comparison of sorted cranial mesoderm (CM) and cranial neural crest (CNC) cells from E9.5 mouse embryos; (2) comparisons of transcription profiles of head tissues from mouse embryos with a CM-specific loss-of-function of Twist1 and control mouse embryos collected at E8.5 and E9.5; (3) ChIP-seq using a TWIST1-specific monoclonal antibody with chromatin extracts from TWIST1-expressing MDCK cells, a model for a TWIST1-dependent mesenchymal state.
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