Journal: bioRxiv

Article Title: Developmental origins of cell heterogeneity in the human lung

doi: 10.1101/2022.01.11.475631

Figure Lengend Snippet: (A) UMAP-plot of proximal clusters and pseudotime of secretory and neuroendocrine (NE) trajectories, estimated by Slingshot. Colors as in . The asterisk: bifurcation point of the 2 NE-clusters. (B) Heatmap of the top-10 markers of each stable gene-module of the 569 differentially expressed genes along the 2 trajectories , according to tradeSeq. (C-E) UMAP-plots showing the aggregate expression of the (C) SCLC-A, (D) SCLC-N and (E) SCLC-Y signature-genes ( Ireland et al ., 2020 ). (F) SCRINSHOT-analysis of NE-clusters, in a 14 pcw proximal airway. Cl-11 markers: GHRL (green), RFX6 (cyan), ACSL1 (yellow). Cl-12 markers: GRP (red), ASCL1 (gray), CALCA (magenta). Dotted outlines: manually segmented nuclei. PROX1, DPP10, SST, VSTM2L, CFC, NKX2-2, SCGB3A2 and EPCAM (italics) only as individual channels. Scale-bar: 10µm. (G) Schematic representation of the suggested NOTCH-signaling function on secretory and NE-cell specification.

Article Snippet: The following primary antibodies were used: anti-PHOX2B goat polyclonal antibody (R&D Systems, AF4940-SP, 2μg/mL), anti-DLL3 rabbit monoclonal antibody (Cell Signaling Technology, 71804, 1:50), anti-NF-M mouse monoclonal antibody (DSHB, 2H3, 2μg/ml), anti-COL13A1 rabbit polyclonal antibody (NovusBio, NBP2-13854, 1:100), Cy3 anti-αSmooth Muscle Actin (ACTA2) mouse monoclonal antibody (Sigma Aldrich, C6198, 1:2000), anti-GHRL rat monoclonal antibody (R&D Systems, MAB8200-SP, 1.25μg/ml), anti-GRP rabbit polyclonal antibody (Bioss, bs-0011R, 1:200), anti-SOX10 goat polyclonal antibody (R&D Systems, AF2864-SP, 5μg/ml), anti-MASH1 rabbit monoclonal antibody (Abcam, ab240385, 1:100), anti-ISL1 mouse monoclonal antibody (DSHB, 40.2D6, 1.3μg/ml), anti-CGRP mouse monoclonal antibody (Santa Cruz, sc57053, 1:250), anti-ACSL1 rabbit polyclonal antibody (Atlas Antibodies, HPA011964, 1:250) and anti-E-cadherin mouse Alexa Flour 555 (BD Biosciences, 560064, 1:100).

Techniques: Expressing

Journal: bioRxiv

Article Title: Developmental origins of cell heterogeneity in the human lung

doi: 10.1101/2022.01.11.475631

Figure Lengend Snippet: (A) RNA velocity analysis of epithelial cells, on the UMAP-plot. Colors as in and arrow direction indicates the future state of the cells. (B) Heatmap of the 569 differentially expressed genes (FDR<0.0001 and FcMedian>1) along the proximal secretory and neuroendocrine (NE) trajectories, based on tradeSeq. The dendrogram (left) indicates 9 stable gene-modules. (C) Balloon-plot of the top-10 selective transcription factors (TFs) in the proximal epithelial secretory and NE-clusters. (D-F) Violin-plots of the transcription factors MYCL (D), NEUROD1 (E) and HNF4G (F), in all epithelial clusters. Expression levels: log 2 (normalized UMI-counts+1) (library size was normalized to 10.000). (G) Balloon-plot of the top-25 selective markers for each NE-cluster compared to the other. Balloon size: percent of positive cells. Color intensity: scaled expression. (H) Bar-plot of the top-10 enriched biological process p-values in epi cl-11 compared to epi cl-12, using its statistically-significant (adjusted p-value <0.001) upregulated genes. (I) as in “H” for epi cl-12, compared to Sam2 as in”L” for epi cl-11. (J) Balloon-plot of the 31 analyzed genes with SCRINSHOT. (K) Balloon-plot of the NE-gene expression changes over time, in epi cl-12, for the common NE-markers: PROX1, DPP10 , epi cl-12 markers: GRP, ASCL1, SST and CALCA and eight epi cl-11 markers GHRL - PCSK1 . (L) Same as in “L” for epi cl-11. Balloon size: percent of positive cells. Color intensity: log 2 (normalized UMI-counts+1) (library size was normalized to 10.000). Blue: high. Gray: zero. (M) Balloon-plot of NOTCH-signaling components ( Ouadah et al ., 2019 ), in addition to the neuronal gene inhibitor REST ( Lim et al ., 2017 ), the TF YAP1 , the secretory marker SCGB3A2 , and the NE-markers MYCL, ASCL1, GRP, NEUROD1 and GHRL . Balloon size: percent of positive cells. Color intensity: scaled expression (N) CellChat hierarchical plot of SST-SSTR2 communication pattern between the two NE-cell states. (O) Balloon-plot of BCL2, CITED and IRF2BP2 expression levels that are included in the top-100 NicheNet predicted SST target-genes. Ligand: blue, Receptor: magenta. Balloon size: percent of positive cells. Color intensity: scaled expression.

Article Snippet: The following primary antibodies were used: anti-PHOX2B goat polyclonal antibody (R&D Systems, AF4940-SP, 2μg/mL), anti-DLL3 rabbit monoclonal antibody (Cell Signaling Technology, 71804, 1:50), anti-NF-M mouse monoclonal antibody (DSHB, 2H3, 2μg/ml), anti-COL13A1 rabbit polyclonal antibody (NovusBio, NBP2-13854, 1:100), Cy3 anti-αSmooth Muscle Actin (ACTA2) mouse monoclonal antibody (Sigma Aldrich, C6198, 1:2000), anti-GHRL rat monoclonal antibody (R&D Systems, MAB8200-SP, 1.25μg/ml), anti-GRP rabbit polyclonal antibody (Bioss, bs-0011R, 1:200), anti-SOX10 goat polyclonal antibody (R&D Systems, AF2864-SP, 5μg/ml), anti-MASH1 rabbit monoclonal antibody (Abcam, ab240385, 1:100), anti-ISL1 mouse monoclonal antibody (DSHB, 40.2D6, 1.3μg/ml), anti-CGRP mouse monoclonal antibody (Santa Cruz, sc57053, 1:250), anti-ACSL1 rabbit polyclonal antibody (Atlas Antibodies, HPA011964, 1:250) and anti-E-cadherin mouse Alexa Flour 555 (BD Biosciences, 560064, 1:100).

Techniques: Expressing, Gene Expression, Marker

Journal: European Journal of Neurology

Article Title: Comparative effectiveness and tolerability of calcitonin gene‐related peptide ( CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real‐world study in Taiwan

doi: 10.1111/ene.16372

Figure Lengend Snippet: Baseline characteristics in chronic migraine patients receiving calcitonin gene‐related peptide monoclonal antibodies and onabotulinumtoxinA.

Article Snippet: According to a report by the Institute for Clinical and Economic Review (ICER), the treatment efficacies of CGRP mAbs and onabotulinumtoxinA were comparable based on network meta‐analysis [ ].

Techniques: Bioprocessing

Journal: European Journal of Neurology

Article Title: Comparative effectiveness and tolerability of calcitonin gene‐related peptide ( CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real‐world study in Taiwan

doi: 10.1111/ene.16372

Figure Lengend Snippet: Treatment outcomes of chronic migraine patients treated with calcitonin gene‐related peptide monoclonal antibodies or onabotulinumtoxinA at 6 months. Least‐squares mean change (standard error) from baseline in the number of monthly migraine days (MMDs) (a) and monthly moderate‐to‐severe migraine days (MMSMDs) (b) and proportions of patients with ≥50% (c) or ≥ 75% (d) reduction in MMDs and MMSMDs at 6 months. CGRP, calcitonin gene‐related peptide; DTT, difficult‐to‐treat; mAb, monoclonal antibody; MMD, monthly migraine day; MMSMD, monthly moderate‐to‐severe migraine day; MOH, medication‐overuse headache; onabotA, onabotulinumtoxinA. *** p ≤ 0.001, ** p ≤ 0.01.

Article Snippet: According to a report by the Institute for Clinical and Economic Review (ICER), the treatment efficacies of CGRP mAbs and onabotulinumtoxinA were comparable based on network meta‐analysis [ ].

Techniques: Bioprocessing

Journal: European Journal of Neurology

Article Title: Comparative effectiveness and tolerability of calcitonin gene‐related peptide ( CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real‐world study in Taiwan

doi: 10.1111/ene.16372

Figure Lengend Snippet: Subgroup analysis in difficult‐to‐treat (DTT) and medication‐overuse headache (MOH) patients. Least‐squares mean change (standard error) from baseline in the number of monthly migraine days (MMDs) (a) at 6 months and ≥ 50% and ≥ 75% responder rates for MMDs (b) in patients who were DTT and those with MOH (c, d). CGRP, calcitonin gene‐related peptide; DTT, difficult‐to‐treat; mAb, monoclonal antibody; MMD, monthly migraine day; MOH, medication‐overuse headache; onabotA, onabotulinumtoxinA. *** p ≤ 0.001, ** p ≤ 0.01, * p < 0.05.

Article Snippet: According to a report by the Institute for Clinical and Economic Review (ICER), the treatment efficacies of CGRP mAbs and onabotulinumtoxinA were comparable based on network meta‐analysis [ ].

Techniques:

Journal: British Journal of Pharmacology

Article Title: Structure of Class B GPCRs: new horizons for drug discovery

doi: 10.1111/bph.12689

Figure Lengend Snippet: Therapeutic applications of Class B receptors and drugs directed at the receptors

Article Snippet: , CGRP peptide mAb , Migraine , ALD403 , Alder Biopharmaceuticals , Ph2.

Techniques: Clinical Proteomics