Developmental Transcriptomic Features of the Carcinogenic Liver Fluke, Clonorchis sinensis

Clonorchis sinensis is the causative agent of the life-threatening disease endemic to China, Korea, and Vietnam. It is estimated that about 15 million people are infected with this fluke. C. sinensis provokes inflammation, epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause cholangiocarcinoma in chronically infected individuals. Accumulation of a large amount of biological information about the adult stage of this liver fluke in recent years has advanced our understanding of the pathological interplay between this parasite and its hosts. However, no developmental gene expression profiles of C. sinensis have been published. In this study, we generated gene expression profiles of three developmental stages of C. sinensis by analyzing expressed sequence tags (ESTs). Complementary DNA libraries were constructed from the adult, metacercaria, and egg developmental stages of C. sinensis. A total of 52,745 ESTs were generated and assembled into 12,830 C. sinensis assembled EST sequences, and then these assemblies were further categorized into groups according to biological functions and developmental stages. Most of the genes that were differentially expressed in the different stages were consistent with the biological and physical features of the particular developmental stage; high energy metabolism, motility and reproduction genes were differentially expressed in adults, minimal metabolism and final host adaptation genes were differentially expressed in metacercariae, and embryonic genes were differentially expressed in eggs. The higher expression of glucose transporters, proteases, and antioxidant enzymes in the adults accounts for active uptake of nutrients and defense against host immune attacks. The types of ion channels present in C. sinensis are consistent with its parasitic nature and phylogenetic placement in the tree of life. We anticipate that the transcriptomic information on essential regulators of development, bile chemotaxis, and physico-metabolic pathways in C. sinensis that presented in this study will guide further studies to identify novel drug targets and diagnostic antigens

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Helium and argon isotope geochemistry of alkaline intrusion-associated gold and copper deposits along the Red River-Jinshajiang fault belt, SW China

The Red River-Jinshajiang strike-slip fault zone on the eastern margin of the Tibetan plateau was originally produced by the India-Eurasia collision ∼60-70 Myr ago. Numerous post-collisional, mantle-derived alkaline igneous rocks, with ages of ∼40-30 Ma, have been intruded along this fault zone. In recent years, several copper and gold deposits associated with the alkaline intrusions of this region were discovered, such as the Yao'an and Beiya gold deposits and the Yulong and Machangqing copper deposits studied in this paper. The mineralised intrusions are felsic, with SiO 2 ranging from 61.4 to 67.7 wt.%, K 2O+Na 2O from 8.1 to 11.5 wt.% and K 2O/Na 2O>1. The deposits are located at both the exo- and endo-contact zones of the intrusions. The mineral deposits are of hydrothermal origin, with the ore-forming temperatures mainly in the range 150-450 °C. This paper presents He and Ar isotope analyses of these four deposits. The concentrations of 4He trapped in fluid inclusions of pyrites from the ores are (0.7-54.1)× 10 -6 cm 3 STP g -1, and those of 40Ar are (0.6-7.3)×10 -6 cm 3 STP g -1, 3He/ 4He ratios are 0.3-2.5 Ra (Ra represents the 3He/ 4He ratio of air, 1.39×10 -6), 40Ar/ 36Ar ratios are 316-1736, and 3He/ 36Ar ratios are 0.2-11.2× 10 -3. Generally, the 3He/ 4He, 40Ar/ 36Ar and 3He/ 36 Ar ratios for the gold deposits are higher than those for the copper deposits. We suggest that the ore-forming fluids of both gold and copper deposits were differentiated from the mantle-derived alkaline magmas, but were diluted by modified air-saturated water (MASW) that experienced intensive interaction with crustal rocks. However, the magmatic fluids responsible for the gold deposits were less extensively diluted by MASW, resulting in higher 3He/ 4He, 40Ar/ 36Ar and 3He/ 36Ar ratios than the copper deposits. © 2003 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex

Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment

Chenchen Bi,1,* Aiping Wang,1,* Yongchao Chu,1 Sha Liu,1 Hongjie Mu,1 Wanhui Liu,1 Zimei Wu,1 Kaoxiang Sun,1 Youxin Li1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co, Ltd., Yantai, People’s Republic of China *These authors contributed equally to this work Abstract: Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. Keywords: rotigotine, lactoferrin-modified PEG-PLGA nanoparticles, brain targeting, intranasal delivery, Parkinson’s diseas

GaN1-xPx ternary alloys with high P composition grown by metal-organic chemical vapor deposition

GaN1-xPx ternary alloys with high P compositions were deposited on sapphire substrates by means of metal-organic chemical vapor deposition. Depth profiles of the elements indicate that the maximum P/N composition ratio is about 17% and a uniform distribution of the P atoms in the alloys is achieved. 2theta/omega XRD spectra demonstrate that the (0002) peak of the GaN1-xPx alloys shifts to smaller angle with increasing P composition. From the photoluminescence (PL) spectra, the red shifts to the bandedge emission of GaN are determined to be 73, 78, 100 and 87 meV for the GaN1-xPx alloys with the P/N composition ratios of 3%, 11%, 15% and 17%, respectively. No PL peak related to GaP is observed, indicating that the phase separation between GaN and GaP is well suppressed in our GaN1-xPx samples. (C) 2003 Elsevier Science B.V. All rights reserved

Phase-separation suppression in GaN-rich side of GaNP alloys grown by metal-organic chemical vapor deposition

The GaN-rich side of GaNP ternary alloys has been successfully synthesized by light-radiation heating and low-pressure metal-organic chemical vapor deposition. X-ray diffraction (XRD) rocking curves show that the ( 0002) peak of GaNP shifts to a smaller angle with increasing P content. From the GaNP photoluminescence (PL) spectra, the red shifts from the band-edge emission of GaN are determined to be 73, 78 and 100 meV, respectively, in the GaNP alloys with the P contents of 1.5%, 5.5% and 7.5%. No PL peak or XRD peak related to GaP is observed, indicating that phase separation induced by the short-range distribution of GaP-rich regions in the GaNP layer has been effectively suppressed. The phase-separation suppression in the GaNP layer is associated with the high growth rate and the quick cooling rate under the given growth conditions, which can efficiently restrain the accumulation of P atoms in the GaNP layer