Sequencing of \u3ci\u3eAspergillus nidulans\u3c/i\u3e and comparative analysis with \u3ci\u3eA. fumigatus\u3c/i\u3e and \u3ci\u3eA. oryzae\u3c/i\u3e

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso, and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation. Document includes all supplementary information (820 pages). Supplementary files are also attached below as Related files. THERE IS NO SUPPLEMENTARY FILE #7. PDF file size (with supplementary files included) is 10 Mbytes. An optimized version of the ARTICLE ONLY is attached as a Related File and is 1.9 Mbytes

Sequencing of \u3ci\u3eAspergillus nidulans\u3c/i\u3e and comparative analysis with \u3ci\u3eA. fumigatus\u3c/i\u3e and \u3ci\u3eA. oryzae\u3c/i\u3e

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso, and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation. Document includes all supplementary information (820 pages). Supplementary files are also attached below as Related files. THERE IS NO SUPPLEMENTARY FILE #7. PDF file size (with supplementary files included) is 10 Mbytes. An optimized version of the ARTICLE ONLY is attached as a Related File and is 1.9 Mbytes

Opposing Regulation of PROX1 by Interleukin-3 Receptor and NOTCH Directs Differential Host Cell Fate Reprogramming by Kaposi Sarcoma Herpes Virus

Lymphatic endothelial cells (LECs) are differentiated from blood vascular endothelial cells (BECs) during embryogenesis and this physiological cell fate specification is controlled by PROX1, the master regulator for lymphatic development. When Kaposi sarcoma herpes virus (KSHV) infects host cells, it activates the otherwise silenced embryonic endothelial differentiation program and reprograms their cell fates. Interestingly, previous studies demonstrated that KSHV drives BECs to acquire a partial lymphatic phenotype by upregulating PROX1 (forward reprogramming), but stimulates LECs to regain some BEC-signature genes by downregulating PROX1 (reverse reprogramming). Despite the significance of this KSHV-induced bidirectional cell fate reprogramming in KS pathogenesis, its underlying molecular mechanism remains undefined. Here, we report that IL3 receptor alpha (IL3Rα) and NOTCH play integral roles in the host cell type-specific regulation of PROX1 by KSHV. In BECs, KSHV upregulates IL3Rα and phosphorylates STAT5, which binds and activates the PROX1 promoter. In LECs, however, PROX1 was rather downregulated by KSHV-induced NOTCH signal via HEY1, which binds and represses the PROX1 promoter. Moreover, PROX1 was found to be required to maintain HEY1 expression in LECs, establishing a reciprocal regulation between PROX1 and HEY1. Upon co-activation of IL3Rα and NOTCH, PROX1 was upregulated in BECs, but downregulated in LECs. Together, our study provides the molecular mechanism underlying the cell type-specific endothelial fate reprogramming by KSHV

Crinipellins A and I, Two Diterpenoids from the Basidiomycete Fungus Crinipellis rhizomaticola, as Potential Natural Fungicides

In the course of screening for microbes with antifungal activity, we found that the culture filtrate of the IUM00035 isolate exhibited strong antifungal activity against Magnaporthe oryzae and Colletotrichum coccodes in planta. Based on the phylogenetic analysis with the ITS region, the IUM00035 isolate was identified as Crinipellis rhizomaticola. To identify antifungal compounds from the C. rhizomaticola IUM00035 isolate, the culture filtrate of the isolate was partitioned with ethyl acetate and n-butanol and, consequently, two active compounds were isolated from the ethyl acetate extract. The chemical structures of the isolated compounds were determined as crinipellin A (1) and a new crinipellin derivative, crinipellin I (2), by NMR spectral analyses and a comparison of their NMR and MS data with those reported in the literature. Crinipellin A (1) exhibited a wide range of antifungal activity in vitro against C. coccodes, M. oryzae, Botrytis cinerea, and Phytophthora infestans (MICs = 1, 8, 31, and 31 µg/mL, respectively). Furthermore, when plants were treated with crinipellin A (1) (500 µg/mL) prior to inoculation with fungal pathogens, crinipellin A (1) exhibited disease control values of 88%, 65%, and 60% compared with non-treatment control against tomato late blight, pepper anthracnose, and wheat leaf rust, respectively. In contrast to crinipellin A (1), crinipellin I (2) showed weak or no activity (MICs > 250 µg/mL). Taken together, our results show that the C. rhizomaticola IUM00035 isolate suppresses the development of plant fungal diseases, in part through the production of crinipellin A (1)

Experimental Investigation of Natural Circulation Instability in a BWR-Type Small Modular Reactor

The Purdue NMR (Novel Modular Reactor) represents a BWR-type small modular reactor with a significantly reduced reactor pressure vessel (RPV). Specifically, the NMR is one third the height and area of a conventional BWR RPV with an electrical output of 50 MWe. Experiments are performed in a well-scaled test facility to investigate the thermal hydraulic flow instabilities during the startup transients for the NMR. The scaling analysis for the design of natural circulation test facility uses a three-level scaling methodology. Scaling criteria are derived from non-dimensional field and constitutive equations. Important thermal hydraulic parameters, e.g. system pressure, inlet coolant flow velocity and local void fraction, are analyzed for slow and fast normal startup transients. Flashing instability and density wave oscillation are the main flow instabilities observed when system pressure is below 0.5 MPa. And the flashing instability and density wave oscillation show different type of oscillations in void fraction profile. Finally, the pressurized startup procedure is recommended and tested in current research to effectively eliminate the flow instabilities during the NMR startup transients

Additional file 1 of p53 activation enhances the sensitivity of non-small cell lung cancer to the combination of SH003 and docetaxel by inhibiting de novo pyrimidine synthesis

Additional file 1. Uncropped western blot band in Figure

Preparation of Polyimide/Graphene Oxide Nanocomposite and Its Application to Nonvolatile Resistive Memory Device

2,6-Diaminoanthracene (AnDA)-functionalized graphene oxide (GO) (AnDA-GO) was prepared and used to synthesize a graphene oxide-based polyimide (PI-GO) by the in-situ polymerization method. A PI-GO nanocomposite thin film was prepared and characterized by infrared (IR) spectroscopy, thermogravimetric analysis (TGA) and UV-visible spectroscopy. The PI-GO film was used as a memory layer in the fabrication of a resistive random access memory (RRAM) device with aluminum (Al) top and indium tin oxide (ITO) bottom electrodes. The device showed write-once-read-many-times (WORM) characteristics with a high ON/OFF current ratio (Ion/Ioff = 3.41 × 108). This excellent current ratio was attributed to the high charge trapping ability of GO. In addition, the device had good endurance until the 100th cycle. These results suggest that PI-GO is an attractive candidate for applications in next generation nonvolatile memory