ENU mutagenesis reveals that Notchless homolog 1 (Drosophila) affects Cdkn1a and several members of the Wnt pathway during murine pre-implantation development

Lossie, Amy C.; Lo, Chiao-Ling; Baumgarner, Katherine; Cramer, Melissa J; Garner, Joseph P.; Justice, Monica J.

doi:10.1186/1471-2156-13-106

Cited by 10 publications

(8 citation statements)

References 53 publications

(83 reference statements)

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“…NLE plays a role in regulating the Notch activity and is involved in embryonic development in mammals by affecting the CDKN1A and Wnt pathways [ 69 ]. Forced expression of miR-26 inhibits the growth of stimulated breast cancer cells and tumor in xenograft models by reducing the mRNA expression levels of AMMECR1 and other genes [ 70 ].…”

Section: Resultsmentioning

confidence: 99%

Similarities in Gene Expression Profiles duringIn VitroAging of Primary Human Embryonic Lung and Foreskin Fibroblasts

Marthandan

Priebe

Baumgart

et al. 2015

BioMed Research International

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Replicative senescence is of fundamental importance for the process of cellular aging, since it is a property of most of our somatic cells. Here, we elucidated this process by comparing gene expression changes, measured by RNA-seq, in fibroblasts originating from two different tissues, embryonic lung (MRC-5) and foreskin (HFF), at five different time points during their transition into senescence. Although the expression patterns of both fibroblast cell lines can be clearly distinguished, the similar differential expression of an ensemble of genes was found to correlate well with their transition into senescence, with only a minority of genes being cell line specific. Clustering-based approaches further revealed common signatures between the cell lines. Investigation of the mRNA expression levels at various time points during the lifespan of either of the fibroblasts resulted in a number of monotonically up- and downregulated genes which clearly showed a novel strong link to aging and senescence related processes which might be functional. In terms of expression profiles of differentially expressed genes with age, common genes identified here have the potential to rule the transition into senescence of embryonic lung and foreskin fibroblasts irrespective of their different cellular origin.

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Section: Resultsmentioning

confidence: 99%

Similarities in Gene Expression Profiles duringIn VitroAging of Primary Human Embryonic Lung and Foreskin Fibroblasts

Marthandan

Priebe

Baumgart

et al. 2015

BioMed Research International

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“…cDNA was PCR amplified in triplicate and Ct values from each sample were obtained using StepOnePlus software. The relative expression of each gene was calculated based on the ΔΔCt value, where the results were normalized to the average Ct value of HPRT1 and UBC (Lossie et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

Biomarker discovery for disease status and symptom severity in children with autism

Oztan

Jackson

Libove

et al. 2018

Psychoneuroendocrinology

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Autism spectrum disorder (ASD) is characterized by social impairments and repetitive behaviors, and affects 1 in 68 US children. Despite ASD's societal impact, its disease mechanisms remain poorly understood. Recent preclinical ASD biomarker discovery research has implicated the neuropeptides oxytocin (OXT) and arginine vasopressin (AVP), and their receptors, OXTR and AVPR1A, in animal models. Efforts to translate these findings to individuals with ASD have typically involved evaluating single neuropeptide measures as biomarkers of ASD and/or behavioral functioning. Given that ASD is a heterogeneous disorder, and unidimensional ASD biomarker studies have been challenging to reproduce, here we employed a multidimensional neuropeptide biomarker analysis to more powerfully interrogate disease status and symptom severity in a well characterized child cohort comprised of ASD patients and neurotypical controls. These blood-based neuropeptide measures, considered as a whole, correctly predicted disease status for 57 out of 68 (i.e., 84%) participants. Further analysis revealed that a composite measure of OXTR and AVPR1A gene expression was the key driver of group classification, and that children with ASD had lower neuropeptide receptor mRNA levels compared to controls. Lower neuropeptide receptor mRNA levels also predicted greater symptom severity for core ASD features (i.e., social impairments and stereotyped behaviors), but were unrelated to intellectual impairment, an associated feature of ASD. Findings from this research highlight the value of assessing multiple related biological measures, and their relative contributions, in the same study, and suggest that low blood neuropeptide receptor availability may be a promising biomarker of disease presence and symptom severity in ASD.

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“…8 Being able to isolate a factor that causes this variation (for example cell culture, PCR plate, or sex) by adding it to the statistical model increases sensitivity in detecting treatment effects and increases power. 10,11,25,30 These nuisance variables can be managed by using a randomized block design that incorporates the nuisance variables as 'blocks'. In mice, the home cage is a good example of a nuisance variable that can be used as a block to control variability from cage to cage.…”

Section: Power As a Performance Standardmentioning

confidence: 99%

Power to the People: Power, Negative Results and Sample Size

Gaskill¹,

Garner²

2020

j am assoc lab anim sci

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The practical application of statistical power is becoming an increasingly important part of experimental design, data analysis, and reporting. Power is essential to estimating sample size as part of planning studies and obtaining ethical approval for them. Furthermore, power is essential for publishing and interpreting negative results. In this manuscript, we review what power is, how it can be calculated, and reporting recommendations if a null result is found. Power can be thought of as reflecting the signal to noise ratio of an experiment. The conventional wisdom that statistical power is driven by sample size (which increases the signal in the data), while true, is a misleading oversimplification. Relatively little discussion covers the use of experimental designs which control and reduce noise. Even small improvements in experimental design can achieve high power at much lower sample sizes than (for instance) a simple t test. Failure to report experimental design or the proposed statistical test on animal care and use protocols creates a dilemma for IACUCs, because it is unknown whether sample size has been correctly calculated. Traditional power calculations, which are primarily provided for animal number justifications, are only available for simple, yet low powered, experimental designs, such as paired t tests. Thus, in most controlled experimental studies, the only analyses for which power can be calculated are those that inheriently have low statistical power; these analyses should not be used because they require more animals than necessary. We provide suggestions for more powerful experimental designs (such as randomized block and factorial designs) that increase power, and we describe methods to easily calculate sample size for these designs that are suitable for IACUC number justifications. Finally we also provide recommendations for reporting negative results, so that readers and reviewers can determine whether an experiment had sufficient power. The use of more sophisticated designs in animal experiments will inevitably improve power, reproducibility, and reduce animal use.

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ENU mutagenesis reveals that Notchless homolog 1 (Drosophila) affects Cdkn1a and several members of the Wnt pathway during murine pre-implantation development

Cited by 10 publications

References 53 publications

Similarities in Gene Expression Profiles duringIn VitroAging of Primary Human Embryonic Lung and Foreskin Fibroblasts

Similarities in Gene Expression Profiles duringIn VitroAging of Primary Human Embryonic Lung and Foreskin Fibroblasts

Biomarker discovery for disease status and symptom severity in children with autism

Power to the People: Power, Negative Results and Sample Size

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