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Background Species of the Apiaceae family produce furanocoumarins—photosensitizing substances widely used in pharmacology. Among them, certain species of the genus Heracleum , commonly known as “giant hogweeds”, are particularly renowned for their photosensitizing properties. While the metabolic composition of these plants has been studied extensively, their genomics remains largely unexplored, as does the biosynthesis of furanocoumarins within the genus. The reasons behind the increased photosensitivity of giant hogweeds compared to other Heracleum species remain unclear. Results A comparison of the genomic features and furanocoumarin content of the aboveground organs in two Heracleum species was carried out: H. sosnowskyi , a giant hogweed with strong photosensitizing activity, and H. sibiricum, a non-invasive and “harmless” species. Both species produce all known angular and linear compounds of the furanocoumarin synthesis pathway (from umbelliferone to isopimpinellin). The genomes of both species possess homologues of genes involved in the biosynthesis of both angular and linear furanocoumarins. However, the two species differ significantly in the quantity of those compounds. H. sibiricum synthesizes angular furanocoumarins in a much lower level, probably due to lack of the gene for umbelliferon-8-dimetylallyl transferase enzyme. H. sosnowskyi accumulates significantly higher level of xanthotoxin. Interpopulation differences were observed in both the compound content and the expression level of biosynthetic genes. Conclusion This study represents the first comparative analysis of genomic and metabolic data for closely related Heracleum species in relation to furanocoumarin biosynthesis. Graphical Abstract Highlights •  H. sosnowskyi contains all compounds of linear/angular furocoumarin synthesis pathway •  H. sibiricum does not synthesize angular furanocoumarins in above-ground organs •  H. sosnowskyi contains more highly expressed homologues of 5- and 8-MOP synthesis • Genomes of both species contain all homologues for furanocoumarin synthesis pathway • Furanocoumarin synthesis is activated in different populations and climate conditions

Inflammatory bowel disease (IBD) is a complex and multifactorial systemic disorder of the gastrointestinal tract and is strongly associated with the development of colorectal cancer. Despite extensive studies of IBD pathogenesis, the molecular mechanism of colitis-driven tumorigenesis is not yet fully understood. In the current animal-based study, we report a comprehensive bioinformatics analysis of multiple transcriptomics datasets from the colon tissue of mice with acute colitis and colitis-associated cancer (CAC). We performed intersection of differentially expressed genes (DEGs), their functional annotation, reconstruction, and topology analysis of gene association networks, which, when combined with the text mining approach, revealed that a set of key overexpressed genes involved in the regulation of colitis (C3, Tyrobp, Mmp3, Mmp9, Timp1) and CAC (Timp1, Adam8, Mmp7, Mmp13) occupied hub positions within explored colitis- and CAC-related regulomes. Further validation of obtained data in murine models of dextran sulfate sodium (DSS)-induced colitis and azoxymethane/DSS-stimulated CAC fully confirmed the association of revealed hub genes with inflammatory and malignant lesions of colon tissue and demonstrated that genes encoding matrix metalloproteinases (acute colitis: Mmp3, Mmp9; CAC: Mmp7, Mmp13) can be used as a novel prognostic signature for colorectal neoplasia in IBD. Finally, using publicly available transcriptomics data, translational bridge interconnecting of listed colitis/CAC-associated core genes with the pathogenesis of ulcerative colitis, Crohn’s disease, and colorectal cancer in humans was identified. Taken together, a set of key genes playing a core function in colon inflammation and CAC was revealed, which can serve both as promising molecular markers and therapeutic targets to control IBD and IBD-associated colorectal neoplasia.

Salinity tolerance in rice, like in other glycophytes, is a function of cellular ion homeostasis. The large divergence in ion homeostasis between the salt-tolerant FL478 and salt-sensitive IR29 rice varieties can be exploited to understand mechanisms of salinity tolerance. Physiological studies indicate that FL478 shows a lower Na+ influx, a reduced Na+ translocation to the shoot, and maintains a lower Na+:K+ ratio. To understand the basis of these differences, a comparative investigation of transcript regulation in roots of the two cultivars was undertaken. This analysis revealed that genes encoding aquaporins, a silicon transporter, and N transporters are induced in both cultivars. However, transcripts for cation transport proteins including OsCHX11, OsCNGC1, OsCAX, and OsTPC1 showed differential regulation between the cultivars. The encoded proteins are likely to participate in reducing Na+ influx, lowering the tissue Na+:K+ ratio and limiting the apoplastic bypass flow in roots of FL478 and are therefore important new targets to improve salt tolerance in rice.

Nearly 3 million people worldwide are coinfected with HIV and HCV. Affordable strategies for prevention are needed. We developed a novel vaccination regimen involving replication-defective and serologically distinct chimpanzee adenovirus (ChAd3, ChAd63) vector priming followed by modified vaccinia Ankara (MVA) boosts, for simultaneous delivery of HCV non-structural (NSmut) and HIV-1 conserved (HIVconsv) region immunogens. We conducted a phase I trial in which 33 healthy volunteers were sequentially enrolled and vaccinated via the intramuscular route as follows: 9 received ChAd3-NSmut [2.5 × 10 vp] and MVA-NSmut [2 × 10 pfu] at weeks 0 and 8, respectively; 8 received ChAdV63.HIVconsv [5 × 10 vp] and MVA.HIVconsv [2 × 10 pfu] at the same interval; 16 were co-primed with ChAd3-NSmut [2.5 × 10 vp] and ChAdV63.HIVconsv [5 × 10 vp] followed at week 8 by MVA-NSmut and MVA.HIVconsv [both 1 × 10 pfu]. Immunogenicity was assessed using peptide pools in ELISpot and intracellular cytokine assays. Vaccine-induced whole blood transcriptome changes were assessed by microarray analysis. All vaccines were well tolerated and no vaccine-related serious adverse events occurred. Co-administration of the prime-boost vaccine regimens induced high magnitude and broad T cell responses that were similar to those observed following immunization with either regimen alone. Median (interquartile range, IQR) peak responses to NSmut were 3,480 (2,728-4,464) and 3,405 (2,307-7,804) spot-forming cells (SFC)/10 PBMC for single and combined HCV vaccinations, respectively ( = 0.8). Median (IQR) peak responses to HIVconsv were 1,305 (1,095-4,967) and 1,005 (169-2,482) SFC/10 PBMC for single and combined HIV-1 vaccinations, respectively ( = 0.5). Responses were maintained above baseline to 34 weeks post-vaccination. Intracellular cytokine analysis indicated that the responding populations comprised polyfunctional CD4 and CD8 T cells. Canonical pathway analysis showed that in the single and combined vaccination groups, pathways associated with antiviral and innate immune responses were enriched for upregulated interferon-stimulated genes 24 h after priming and boosting vaccinations. Serologically distinct adenoviral vectors encoding HCV and HIV-1 immunogens can be safely co-administered without reducing the immunogenicity of either vaccine. This provides a novel strategy for targeting these viruses simultaneously and for other pathogens that affect the same populations. https://clinicaltrials.gov, identifier: NCT02362217.

Lung Squamous Cell Carcinoma (SCC) is a Non-Small Cell Lung Cancer (NSCLC) subtype with a strong clinical association with smoking habits and a very low incidence in never-smokers. Molecular profiling of SCC in never-smokers could unveil tumor vulnerabilities and new treatment strategies. We considered a patient cohort of 17 former or current smokers (51.5%) and 16 never-smoker SCC patients (48.5%). TruSight Oncology 500, investigating hotspots in 523 cancer-related genes, Tumor mutation burden (TMB) and microsatellite instability (MSI), and RNA sequencing was performed on tumor tissue. Genomic and transcriptomic profiles were compared between smokers and never-smoker patients. The most frequently altered genes were (67%), (20%) and (17%), with no substantial differences between groups, except for which was more frequently mutated in smokers (86.7% vs 46.7%, p = 0.05), who also showed a higher TMB with respect to non-smokers (median 11 mut/Mb vs 5.5 mut/Mb, p = 0.028); all patients were stable for MSI score (median 1.87 vs 1.82, p = 0.87). Activating mutations in and were found in one and two never-smokers, respectively. Three smoker patients had simultaneous amplifications in and . Enrichment analyses showed that cyclin-dependent protein Ser/Thr kinase activity and PI3K signaling pathways were affected in both groups, while cellular damage response was exclusively altered in never-smokers. Unsupervised hierarchical clustering on transcriptomes effectively identified different specific transcriptional subtypes between smokers and never-smokers. Gene set enrichment analysis highlighted that tumors from never-smokers are characterized by dysregulation in cell membrane potential and ion homeostasis across cell membrane pathways. Genomic and transcriptomic profiles deeply differentiate SCC occurring in never-smokers with respect to SCC in smoker patients. Moreover, SCC could carry canonical NSCLC) activating mutations. Our data suggest that deep molecular analyses resolve tumor heterogeneity and may help with new algorithm-based treatment strategies for SCC.

'Omics' data have increased very rapidly in quantity and resolution, and are increasingly recognized as very valuable experimental observations in the systematic study of biological phenomena. The increase in availability, complexity and nonexpert interest in such data requires the urgent development of accurate and efficient dimensionality reduction and visualization techniques. To illustrate this need for new approaches we extensively discuss current methodology in terms of the limitations encountered. We then illustrate a recent example of how combinations of existing techniques can be used to overcome some of the present limitations, and discuss possible future directions for research in this important field of study.