The chemosensitivity of ovarian cancer patients with a low expression of ERCC1 is better than that of patients with a high expression.Testicular germ cell tumours (TGCTs) respond well to cisplatin-based therapy. However, cisplatin resistance and poor outcomes do occur. It has been suggested that a shift towards DNA hypermethylation mediates cisplatin resistance in TGCT cells, although there is little direct evidence to support this claim. Here we utilized a series of isogenic cisplatin-resistant cell models and observed a strong association between cisplatin resistance in TGCT cells and a net increase in global CpG and non-CpG DNA methylation spanning regulatory, intergenic, genic and repeat elements. Hypermethylated loci were significantly enriched for repressive DNA segments, CTCF and RAD21 sites and lamina associated domains, suggesting that global nuclear reorganization of chromatin structure occurred in resistant cells. Hypomethylated CpG loci were significantly enriched for EZH2 and SUZ12 binding and H3K27me3 sites. Integrative transcriptome and methylome analyses showed a strong negative correlation between gene promoter and CpG island methylation and gene expression in resistant cells and a weaker positive correlation between gene body methylation and gene expression. A bidirectional shift between gene promoter and gene body DNA methylation occurred within multiple genes that was associated with upregulation of polycomb targets and downregulation of tumour suppressor genes. These data support the hypothesis that global remodelling of DNA methylation is a key factor in mediating cisplatin hypersensitivity and chemoresistance of TGCTs and furthers the rationale for hypomethylation therapy for refractory TGCT patients.Spliceosomes are large complexes regulating pre-mRNA processing in eukaryotes. Arabidopsis JANUS encodes a putative subunit of spliceosome`. We recently demonstrated that JANUS plays an essential role during early embryogenesis and root meristem development. Instead of mediating pre-mRNA splicing as a subunit of spliceosome, JANUS regulates the transcription of key genes by recruiting RNA Polymerase II (Pol II). Here, we summarize our latest findings and provide insights into the regulation of JANUS during Arabidopsis development.Preexposure prophylaxis (PrEP) is an effective HIV prevention tool, although effectiveness is dependent upon adherence. It is important to characterize the impact of PrEP on HIV antibody responses in people who experience breakthrough infections to understand the potential impact on timely diagnosis and treatment. Longitudinal HIV-1-specific antibody responses were evaluated in 42 people who inject drugs (PWID) from the Bangkok Tenofovir Study (BTS) (placebo = 28; PrEP = 14) who acquired HIV while receiving PrEP. HIV-1 antibody levels and avidity to three envelope proteins (gp41, gp160, and gp120) were measured in the plasma using a customized Bio-Plex (Bio-Rad Laboratories, Hercules, CA) assay. A time-to-event analysis was performed for each biomarker to compare the distribution of times at which study subjects exceeded the recent/long-term assay threshold, comparing PrEP and placebo treatment groups. We fit mixed-effects models to identify longitudinal differences in antibody levels and avidity between groups. Overall, longitudinal antibody levels and avidity were notably lower in the PrEP breakthrough group compared to the placebo group. Time-to-event analyses demonstrated a difference in time to antibody reactivity between treatment groups for all Bio-Plex biomarkers. Longitudinal gp120 antibody levels within the PrEP breakthrough group were decreased compared to the placebo group. When accounting for PrEP adherence, both gp120 and gp160 antibody levels were lower in the PrEP breakthrough group compared to the placebo group. We demonstrate hindered envelope antibody maturation in PWID who became infected while receiving PrEP in the BTS, which has significant implications for HIV diagnosis. Delayed maturation of the antibody response to HIV may increase the time to detection for antibody-based tests. Clinical Trial Registration Number, NCT00119106.Strigolactones (SLs) and smoke-derived Karrikins (KARs) are structurally similar butenolide compounds that control distinct aspects of plant development. They are perceived by two closely related α/β hydrolases D14 and KAI2, respectively. Responses to both molecules involve the F-box protein MAX2 that participates in the Skp1-Cullin-F-box (SCF) complex, which ubiquitylates developmental regulators of the SMXL family to mark them for degradation by the 26S proteasome, enabling SL and KAR responses. Current research on SL and KAR signaling uses the synthetic molecules rac-GR24, KAR1 and KAR2 for pharmacological treatments. Androgen Receptor Antagonist In a previous microarray analysis, we observed transcriptional activation in response to rac-GR24 in Lotus japonicus seedling roots. We retested transcript accumulation of selected genes by quantitative PCR in the wild type and the max2-4 mutant, and found that surprisingly, a number of them respond to rac-GR24 in a MAX2-independent manner, and also respond in roots of d14 and kai2a kai2b double mutants. Thus, the synthetic compounds induce transcriptional responses independent of their perception by the canonical receptor complex.Phenotypic plasticity is a key component of the ability of organisms to respond to changing environmental conditions. In this study, we aimed to study the establishment of DNA methylation marks in response to an environmental stress in rainbow trout and to assess whether these marks depend on the genetic background. The environmental stress chosen here was temperature, a known induction factor of epigenetic marks in fish. To disentangle the role of epigenetic mechanisms such as DNA methylation in generating phenotypic variations, nine rainbow trout isogenic lines with no genetic variability within a line were used. For each line, half of the eggs were incubated at standard temperature (11°C) and the other half at high temperature (16°C), from eyed-stage to hatching. In order to gain a first insight into the establishment of DNA methylation marks in response to an early temperature regime (control 11°C vs. heated 16°C), we have studied the expression of 8 dnmt3 (DNA methyltransferase) genes, potentially involved in de novo methylation, and analysed global DNA methylation in the different rainbow trout isogenic lines using LUMA (LUminometric Methylation Assay).