Journal: bioRxiv

Article Title: Chromosome (mis)segregation is biased by kinetochore size

doi: 10.1101/278572

Figure Lengend Snippet: ( A ) High spatial and temporal resolution analysis of error correction after monastrol washout in live Indian muntjac fibroblasts stably expressing CENP-A-GFP (green) and treated with 20 nM SiR-tubulin (magenta). Dashed box highlights a region with a chromosome with a large kinetochore pair (indicated by green arrows in the lower panel). Lower panels show corresponding 1.5x zoom images, plus additional time frames. Note the changes in the conformation of the large kinetochore pair, which lags behind during anaphase, but eventually segregates to the correct daughter. Scale bar = 5 μm. Time = min:sec. ( B ) STED/Confocal image of an IM fibroblast in prometaphase after monastrol washout and immunofluorescence to reveal microtubules (α-tubulin, magenta), chromosomes (DAPI, white) and kinetochores (ACA, green). Dashed arrows indicate one chromosome near each pole with syntelic attachments. ( C ) Quantification of erroneous syntelic and merotelic attachments on chromosomes with small or large kinetochores (KTs) in IM fibroblasts after monastrol washout into Aurora B inhibitor and MG-132. ( D ) Quantification of Aurora B activity at kinetochores of IM as inferred by fluorescence intensity quantification of pKNL1 relative to anti-centromere antibodies (ACA) and normalized for the kinetochore area. There are no statistically significant differences. ( E ) STED/Confocal image of an IM fibroblast in anaphase after monastrol washout and immunofluorescence to reveal microtubules (α-tubulin, magenta), chromosomes (DAPI, white) and kinetochores (ACA, green). A merotelic attachment on a lagging chromatid containing a large kinetochore is indicated (dashed box and arrow). Scale bar = 5 μm. The image on the right shows the corresponding 4x zoom. ( F ) Frequencies of anaphase cells with lagging chromosomes in control IM fibroblasts, monastrol washout into MEM medium and monastrol washout into MEM medium with Aurora B inhibitor. ( G ) Frequencies of anaphase cells with at least 1 lagging chromosome with small or large kinetochores (KTs) after monastrol washout, respectively.

Article Snippet: Initially, cells were incubated for 12h with 100 μM monastrol (Tocris bioscience) and after that washed out into MEM medium or MEM containing 1μM Aurora B inhibitor (ZM447439, Selleckchem.com) or MEM containing 1μM Aurora B inhibitor and 20 μM MG-132, a proteasome inhibitor (Calbiochem), based on previous reports ( 34 ).

Techniques: Stable Transfection, Expressing, Immunofluorescence, Activity Assay, Fluorescence

Journal: Psychopharmacology

Article Title: Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels

doi: 10.1007/s00213-017-4569-x

Figure Lengend Snippet: Effects of selective MAO inhibition on monoamine levels in a OFC, b DRN, c BLA, and d dorsomedial striatum (pmol/mg tissue). In c and d , dopamine levels are shown on the left y -axis while NA and 5-HT levels are shown on the right y -axis. Data are mean values ± SEM. Significance is denoted as follows: * p < 0.05, ** p < 0.005 versus vehicle, + p < 0.05 versus lazabemide. e Coronal sections showing regions of interest for ex vivo neurochemical analysis of monoamines following vehicle, moclobemide, and lazabemide administration. dmPFC dorsomedial PFC, OFC orbitofrontal cortex, dmS dorsomedial striatum, NAcb nucleus accumbens, BLA basolateral amygdala, CA1 hippocampal CA1 region, LH lateral hypothalamus, DRN dorsal raphé nuclei. Adapted from Paxinos and Watson

Article Snippet: Moclobemide and lazabemide hydrochloride were purchased from Tocris (UK) and dissolved in 15% hydroxypropyl-beta-cyclodextrin and 0.9% saline (“vehicle”).

Techniques: Inhibition, Ex Vivo

Journal: Psychopharmacology

Article Title: Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels

doi: 10.1007/s00213-017-4569-x

Figure Lengend Snippet: Final group sizes for animals that successfully completed the task under drug conditions

Article Snippet: Moclobemide and lazabemide hydrochloride were purchased from Tocris (UK) and dissolved in 15% hydroxypropyl-beta-cyclodextrin and 0.9% saline (“vehicle”).

Techniques:

Journal: Psychopharmacology

Article Title: Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels

doi: 10.1007/s00213-017-4569-x

Figure Lengend Snippet: Effects of moclobemide ( n = 18) and lazabemide ( n = 21) on total trials to achieve criterion ( a , b ) and the proportion of perseverative errors ( c , d ). Mean values ± SEM for a single post drug administration session are shown. Significance is denoted as follows: * p < 0.05, ** p < 0.01, *** p < 0.001 versus vehicle

Article Snippet: Moclobemide and lazabemide hydrochloride were purchased from Tocris (UK) and dissolved in 15% hydroxypropyl-beta-cyclodextrin and 0.9% saline (“vehicle”).

Techniques:

Journal: Psychopharmacology

Article Title: Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels

doi: 10.1007/s00213-017-4569-x

Figure Lengend Snippet: Effects of moclobemide ( n = 16) and lazabemide ( n = 20) on response latencies (s) following an incorrect ( a , b ) and correct ( c , d ) response. Data for two animals was not saved due to a technical failure with the equipment. * p < 0.05, ** p < 0.01, *** p < 0.001 versus vehicle

Article Snippet: Moclobemide and lazabemide hydrochloride were purchased from Tocris (UK) and dissolved in 15% hydroxypropyl-beta-cyclodextrin and 0.9% saline (“vehicle”).

Techniques:

Journal: Psychopharmacology

Article Title: Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels

doi: 10.1007/s00213-017-4569-x

Figure Lengend Snippet: Lose-shift probabilities for high ( n = 5) and low ( n = 5) perseveration rats that received moclobemide (16 mg/kg, 3 mg/kg), combination of lazabemide and moclobemide, and vehicle

Article Snippet: Moclobemide and lazabemide hydrochloride were purchased from Tocris (UK) and dissolved in 15% hydroxypropyl-beta-cyclodextrin and 0.9% saline (“vehicle”).

Techniques:

Journal: Psychopharmacology

Article Title: Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels

doi: 10.1007/s00213-017-4569-x

Figure Lengend Snippet: Levels of DA and 5-HT in regions of interest following vehicle (Veh, n = 5), lazabemide (L10, n = 6), and moclobemide (M3, n = 4; M16, n = 4) administration

Article Snippet: Moclobemide and lazabemide hydrochloride were purchased from Tocris (UK) and dissolved in 15% hydroxypropyl-beta-cyclodextrin and 0.9% saline (“vehicle”).

Techniques:

Journal: Advanced Science

Article Title: BCR::ABL1‐Induced Enhancer Reprogramming Uncovers Hypersensitivity of Ph+B‐ALL Cells to Enhancer‐Targeting Drugs

doi: 10.1002/advs.202517231

Figure Lengend Snippet: Enhancer‐promoter interactions define Ph+B‐ALL identity and mirror Ph+B‐ALL‐specific gene expression. (A) Principal component analysis (PCA) of H3K27ac ChIP‐Seq signals from cell lines and primary leukemia cells from patients for the indicated leukemia subtypes is shown. PCA analysis was performed using exclusively H3K27ac signals at promoters (left) or at non‐promoter regions (right). Leukemia subtypes of cell lines were defined using cytogenetic and phenotypic data from DSMZ. Data on KMT2A::AFF1 + B‐ALL cells, including ptMLL::AF4 were obtained from GSE74812 , GSE71616 & GSE135024 , while data on Ph+B‐ALL patients (i.e., BAL0A, BAL05, BAL08, BAL11) were generated by this study. (B) Arc plots of PCHi‐C interactions (purple lines) are shown for genes that show leukemia‐ and/or lineage‐specific PCHi‐C interactions. PCHi‐C data on three Ph+B‐ALL samples (BAL08 = patient, TOM‐1/SUP‐B15 = cell lines), and from healthy B‐cell precursors (BCPs) as well as Ph+ myeloid leukemia cells (K562) are shown. H3K27ac ChIP‐Seq custom (blue) tracks are added where available. Custom tracks were generated using the WashU epigenome browser and only interactions that start and end in the depicted area are shown. (C) A cluster dendrogram (top) and PCA plot (bottom) is shown using ‘Ph+B‐ALL CORE interactions’ that allow separation of Ph+B‐ALL cells from healthy BCPs and Ph+ myeloid leukemia cells. (D) A summary of the H3K27ac HiChIP experiment is shown. (E) PCA plots are shown for H3K27ac HiChIP defined enhancer‐promoter interactions (EPIs, top) and enhancer‐enhancer interactions (EEIs) for patient‐derived xenograft (PDX) Ph+ (n = 3) and KMT2A::AFF1 (n = 3) B‐ALL cells. (F) A comparison of H3K27ac HiChIP defined EPIs and respective gene expression is shown, using log2FC values of EPIs per gene versus the expression of the respective genes for Ph+B‐ALL compared to KMT2A::AFF1 + B‐ALL. B‐ALL patient data from the TARGET study was used for patient‐specific gene expression.

Article Snippet: HiChIP was performed using the Arima Genomics HiChIP kit with the recommended protocol.

Techniques: Gene Expression, ChIP-sequencing, Generated, HiChIP, Derivative Assay, Comparison, Expressing

Journal: bioRxiv

Article Title: Chromatin architecture and physical constriction cooperate in phenotype switching and cancer cell dissemination

doi: 10.64898/2026.02.05.702638

Figure Lengend Snippet: a. Seurat UMAP representing the bridge integration of melanoma cell states between scRNAseq (left) and loHiC (right) obtained from a cell derived xenograft (CDX) of 12-273BM short-term patients’ culture. b. cis compartment interactions quantified in MEL and MES states identified in CDX tumors. c. Column dot plot showing the quantification of the number (left) and size (right) of TADs in MEL and MES states by loHiC. d. Genome-wide insulation score profile at TADs’ boundaries in loHiC MEL and MES states. e. TADs’ number (left) and size (right) quantified in a small cohort of FFPE MEL (n=3) and MES (n=4) tumors processed with HiC. Unpaired t-test was conducted and resulted p-values are shown. Each dot represent a patient sample.

Article Snippet: Next, FFPE samples were processed with the Arima-HiC+ FFPE Kit (Arima Genomics, #A101060) following manufacturer’s instructions.

Techniques: Derivative Assay, Genome Wide, Insulation

Journal: bioRxiv

Article Title: Chromatin architecture and physical constriction cooperate in phenotype switching and cancer cell dissemination

doi: 10.64898/2026.02.05.702638

Figure Lengend Snippet: a. Quantification of the number of CNVs as a grouped column plot across MEL, siNTC, siMS, INT and MES samples. Two-way ANOVA test was conducted. b. Column dot plot of the number of structural variants (SVs) found in the melanoma cell lines used in this study. One-way ANOVA test was performed. c. Fraction of cis -short, cis -long and trans HiC contacts in siNTC and siMS cells. Paired t-test was used. d. HiC aggregate region analysis at all TSS in siMS relative to siNTC. e. PCA plot of the most variable cCREs identified with DESeq2. f. ABC quantification of the top 500 state-specific cCRE Hubs across all cell lines. Bar plots show the average of all hubs. Standard error of the means bar are shown. Red, grey and green mark melanocytic, intermediate and mesenchymal cell lines respectively. g. Bar dot plot quantify the average methylation of 500 MES hubs in TCGA melanoma patients (n=470) classified in MEL, INT, NC (neural crest) and MES according to Tsoi . One-way ANOVA p-value summarizing NC and MES vs INT and MEL comparisons is shown. h. HiC aggregate pile up heatmap of contacts at MES hubs in FFPE patients’ specimen classified in MEL (n=3) and MES (n=4). i. Quantification of HiC contacts at the foreground of MEL and MES hubs in MEL and MES melanoma patients (n=7). Unpaired t-test p-values are shown. j. CTCF average genomic occupancy at MES hubs (n=500) in individual mesenchymal cell lines. k. Volcano plot of the differential MES cCREs activity in siCTCF MM099 cells predicted by RNAseq. In blue are marked the significantly dysregulated cCREs, in red the hubs. Y-axis dotted line show the significant p-value threshold. On top are marked the number of significantly active MES hubs (42 down, 136 up). Multiple t-test with Benjamini/Hochberg correction was used. For panels a,b,c,e,g and j, each dot is representative of a biological replicate.

Article Snippet: Next, FFPE samples were processed with the Arima-HiC+ FFPE Kit (Arima Genomics, #A101060) following manufacturer’s instructions.

Techniques: Methylation, Activity Assay, RNA sequencing