Journal: Environmental science & technology

Article Title: High-Throughput Screening and Quantitative Chemical Ranking for Sodium Iodide Symporter (NIS) Inhibitors in ToxCast Phase I Chemical Library

doi: 10.1021/acs.est.7b06145

Figure Lengend Snippet: Examples of chemical responses: A) sodium perchlorate, B) triphenyltin hydroxide, C) folpet. Cell viability and RAIU assay results are illustrated in red and blue respectively. The red and blue horizontal dotted lines represent the 3bMAD threshold for cell viability and RAIU assay respectively. Toxicity-adjusted area (TAA) is the gray striped area defined by 1) maximum concentration vertical line (right border), 2) the 3bMAD significant threshold horizontal line for RAIU assay (top border; blue dashed line), 3) the dose-response curve of RAIU and 4) if present, the dose-response curve of cell viability. The difference of median responses of RAIU and cell viability at maximum tested concentration (Median-Difference) is indicated by the green vertical dotted line. Sodium perchlorate (A) was chosen as the reference NIS inhibitor to normalize test chemical TAA and Median-Difference as percentage values. Ranking score is obtained as the sum of normalized TAA and Median-Difference values. Therefore, sodium perchlorate has a ranking score of 200. B and C show three test chemicals with less RAIU inhibition and more cytotoxicity relative to sodium perchlorate. As the TAA and Median-Difference values decrease, their ranking scores also decrease.

Article Snippet: All control chemicals were initially solubilized in DMSO (EMD Millipore Corp., Darmstadt, Germany) at 20mM and included sodium perchlorate (NaClO 4 ; RAIU assay positive control), sodium nitrate (NaNO 3 ; RAIU assay EC 80 control), sodium thiocyanate (NaSCN; RAIU assay EC 20 control), 2,4-dichlorophenoxyacetic acid (2,4-D; RAIU assay negative control), and 2,3-dichloro-1,4-napthoquinone (DCNQ; cell viability assay positive control) (Sigma Aldrich, St. Louis, MO).

Techniques: Concentration Assay, Inhibition

Journal: Environmental science & technology

Article Title: High-Throughput Screening and Quantitative Chemical Ranking for Sodium Iodide Symporter (NIS) Inhibitors in ToxCast Phase I Chemical Library

doi: 10.1021/acs.est.7b06145

Figure Lengend Snippet: The vertical dotted line is the ranking score of sodium perchlorate, which was used as the reference chemical in the ranking analysis. The ranking score of the 137 test chemical samples ranged from 150.41 to −29.52, with 4 having ranking score >100, 17 having ranking score between 50 and 100, and 116 having ranking score <50. The 46 chemicals that produced significant RAIU inhibition without any significant cytotoxicity at one or two concentrations are marked in green.

Article Snippet: All control chemicals were initially solubilized in DMSO (EMD Millipore Corp., Darmstadt, Germany) at 20mM and included sodium perchlorate (NaClO 4 ; RAIU assay positive control), sodium nitrate (NaNO 3 ; RAIU assay EC 80 control), sodium thiocyanate (NaSCN; RAIU assay EC 20 control), 2,4-dichlorophenoxyacetic acid (2,4-D; RAIU assay negative control), and 2,3-dichloro-1,4-napthoquinone (DCNQ; cell viability assay positive control) (Sigma Aldrich, St. Louis, MO).

Techniques: Produced, Inhibition

Journal: Nature medicine

Article Title: Exome-wide evaluation of rare coding variants using electronic health records identifies new gene-phenotype associations

doi: 10.1038/s41591-020-1133-8

Figure Lengend Snippet: List of robust exome-by-phenome-wide significant gene-phenotype associations. List of genes among 97 pLOF-based gene burdens with phenotype associations at P < 10 −6 in the PMBB discovery cohort that were most robust according to the DiCE approach, which integrates successful replication of the association with clinical and experimental evidence. For replication studies, gene–phenotype associations were evaluated for their robustness by interrogating REVEL-informed missense-based gene burdens and single variants in the same discovery PMBB cohort, and pLOF-based gene burdens, REVEL-informed missense-based gene burdens and single variants in an independent cohort of African Americans in the PMBB (the PMBB2 cohort), as well as in BioMe, DiscovEHR and the UKB. Targeted single variants that showed successful replication in the PMBB, PMBB2 and UKB were additionally analyzed in BioVU. Each gene–phecode association is labeled with the corresponding P value from logistic regression analyses in the discovery phase in the PMBB, as well as the number of total replications and existence of clinical/experimental evidence, fully detailed in Supplementary Table 17 . Only associations with at least two total check marks in Supplementary Table 17 , where each successful mode of replication in a particular biobank (for example, pLOF burden in BioMe) or the existence of clinical/experimental evidence is labeled with a checkmark, were deemed robust and therefore included here. Previously known associations were considered to represent positive controls. Positive control (above line) and new associations (below line) are each ranked alphabetically by gene name.

Article Snippet: 54 Immunolocalization of PPP1R13L in human retina To study the localization of PPP1R13L protein in different retinal layers of the human eye, we performed immunofluorescence on formalin-fixed paraffin-embedded section (N=3) obtained from normal 68-year old donor’s cadaver eyes with a commercially available antibody, anti-PPP1R13L (Cat# 51141-1-AP, Proteintech, IL, USA).

Techniques: Labeling, Positive Control, Coagulation

Journal: Nature medicine

Article Title: Exome-wide evaluation of rare coding variants using electronic health records identifies new gene-phenotype associations

doi: 10.1038/s41591-020-1133-8

Figure Lengend Snippet: A) Differential expression profile of Ppp1r13l transcript in mouse optic nerve head (ONH) with varying stages of intraocular pressure (IOP)-induced glaucoma. Data represent the fold change in Ppp1r13l expression between different stages of D2 mice (glaucoma, N=50 mice) and D2 Gpnmb+ samples (control, N=10 mice). B) Localization of PPP1R13L protein in the human retina. Shown is the distribution of PPP1R13L by immunohistochemical localization in the retina from normal 68-year-old donor eyes. Overlay of images from DAPI (blue; nuclei) and PPP1R13L (red) in adult human retinal layers are shown on the right. The left represents primary antibody control. Scale bars are shown in each image. The experiment was performed twice independently with consistent results. ONL, outer nuclear layer; OPL, outer plexiform layer; IPL, inner plexiform layer; GCL, ganglion cell layer. C) Relative expression of PPP1R13L transcript in response to oxidative stress in induced pluripotent stem cell-derived retinal ganglion cells (iPSC-RGCs). A two-tailed unpaired Student’s t test was used for statistical analysis, and significant p values are shown. Expression of PPP1R13L in iPSC-RGCs is shown under increasing concentrations of H2O2 treatment (N=3 independent experiments per condition). Plotted are the mean fold changes in comparison to no H2O2, error bars represent standard error of the mean (SEM), and individual values are plotted overlaying the bar plot.

Article Snippet: 54 Immunolocalization of PPP1R13L in human retina To study the localization of PPP1R13L protein in different retinal layers of the human eye, we performed immunofluorescence on formalin-fixed paraffin-embedded section (N=3) obtained from normal 68-year old donor’s cadaver eyes with a commercially available antibody, anti-PPP1R13L (Cat# 51141-1-AP, Proteintech, IL, USA).

Techniques: Functional Assay, Biomarker Discovery, Quantitative Proteomics, Expressing, Control, Immunohistochemical staining, Derivative Assay, Two Tailed Test, Comparison