Acting via a cell surface receptor, tetrac and tetrac NP inhibit growth of h-MTC cells and associated angiogenesis in CAM and mouse xenograft models.

No abstract

Rhizopus oryzae causes tobacco pole rot in China during tobacco flue-curing. Fluecuring is a post-harvest process done to prepare tobacco leaves and involves three different stages: the yellowing stage has the lowest temperatures and highest humidity, then the color-fixing stage has higher temperatures and medium humidity, and finally the stem-drying stage has the highest temperatures and lowest humidity. In this study, fungal culturing and IonS5XL high-throughput sequencing techniques were used to reveal the fungal community of the petioles and lamina of tobacco leaves infected with pole rot during flue-curing. A total of 108 fungal isolates belonging to 6 genera were isolated on media. The most common fungal species isolated was the pathogen, R. oryzae, that was most often found equally on petioles and laminas in the color-fixing stage, followed by saprotrophs, mostly Aspergillus spp. High-throughput sequencing revealed saprotrophs with Alternaria being the most abundant genus, followed by Phoma, Cercospora, and Aspergillus, whereas Rhizopus was the tenth most abundant genus, which was mostly found on petioles at the yellowing stage. Both culturable fungal diversity and fungal sequence diversity was higher at stem-drying stage than the yellowing and color-fixing stages, and diversity was higher with leaf lamina than petioles revealing that the changes in fungal composition and diversity during the curing process were similar with both methods. This study demonstrates that the curing process affects the leaf microbiome of tobacco during the curing process, and future work could examine if any of these saprotrophic fungi detected during the curing of tobacco leaves may be potential biocontrol agents for with pole rot in curing chambers.

No abstract

the mechanistic relevance of intergenic disease-associated genetic loci (IDAGL) containing highly statistically significant disease-linked SNPs remains unknown. Here, we present experimental and clinical evidence supporting the importantance of the role of IDAGL in human diseases. A targeted rt-PCr screen coupled with sequencing of purified PCr products detects widespread transcription at multiple IDAGL and identifies 96 small noncoding trans-regulatory rNAs of ~100-300 nt in length containing SNPs (snprNAs) associated with 21 common disorders. Multiple independent lines of experimental evidence support functionality of snprNAs by documenting their cell type-specific expression and evolutionary conservation of sequences, genomic coordinates and biological effects. Chromatin state signatures, expression profiling experiments and luciferase reporter assays demonstrate that many IDAGL are Polycomb-regulated long-range enhancers. expression of snprNAs in human and mouse cells markedly affects cellular behavior and induces allele-specific clinically relevant phenotypic changes: NLRP1-locus snprNAs rs2670660 exert regulatory effects on monocyte/macrophage transdifferentiation, induce prostate cancer (PC) susceptibility snprNAs and transform lowmalignancy hormone-dependent human PC cells into highly malignant androgen-independent PC. Q-PCr analysis and luciferase reporter assays demonstrate that snprNA sequences represent allele-specific "decoy" targets of microrNAs that function as SNP allele-specific modifiers of microrNA expression and activity. We demonstrate that trans-acting rNA molecules facilitating resistance to androgen depletion (rAD) in vitro and castration-resistant phenotype (CrP) in vivo of PC contain intergenic 8q24-locus SNP variants (rs1447295; rs16901979; rs6983267) that were recently linked with increased risk of PC. Q-PCr analysis of clinical samples reveals markedly increased and highly concordant (r = 0.896; p < 0.0001) snprNA expression levels in tumor tissues compared with the adjacent normal prostate [122-fold and 45-fold in Gleason 7 tumors (p = 0.03); 370-fold and 127-fold in Gleason 8 tumors (p = 0.0001) for NLRP1-locus and 8q24-locus snprNAs, respectively]. Our experiments indicate that rAD and Cr phenotype of human PC cells can be triggered by ncrNA molecules transcribed from the NLRP1-locus intergenic enhancer at 17p13 and by downstream activation of the 8q24-locus snprNAs. Our results define the IDAGL at 17p13 and 8q24 as candidate regulatory loci of rAD and Cr phenotypes of PC, reveal previously unknown molecular links between the innate immunity/inflammasome system and development of hormone-independent PC and identify novel molecular and genetic targets with diagnostic and therapeutic potentials, exploration of which should be highly beneficial for personalized clinical management of PC. Networks of intergenic long-range enhancers