Sequencing and analysis of the gastrula transcriptome of the brittle star Ophiocoma wendtii

Background The gastrula stage represents the point in development at which the three primary germ layers diverge. At this point the gene regulatory networks that specify the germ layers are established and the genes that define the differentiated states of the tissues have begun to be activated. These networks have been well-characterized in sea urchins, but not in other echinoderms. Embryos of the brittle star Ophiocoma wendtii share a number of developmental features with sea urchin embryos, including the ingression of mesenchyme cells that give rise to an embryonic skeleton. Notable differences are that no micromeres are formed during cleavage divisions and no pigment cells are formed during development to the pluteus larval stage. More subtle changes in timing of developmental events also occur. To explore the molecular basis for the similarities and differences between these two echinoderms, we have sequenced and characterized the gastrula transcriptome of O. wendtii. Methods Development of Ophiocoma wendtii embryos was characterized and RNA was isolated from the gastrula stage. A transcriptome data base was generated from this RNA and was analyzed using a variety of methods to identify transcripts expressed and to compare those transcripts to those expressed at the gastrula stage in other organisms. Results Using existing databases, we identified brittle star transcripts that correspond to 3,385 genes, including 1,863 genes shared with the sea urchin Strongylocentrotus purpuratus gastrula transcriptome. We characterized the functional classes of genes present in the transcriptome and compared them to those found in this sea urchin. We then examined those members of the germ-layer specific gene regulatory networks (GRNs) of S. purpuratus that are expressed in the O. wendtii gastrula. Our results indicate that there is a shared ‘genetic toolkit’ central to the echinoderm gastrula, a key stage in embryonic development, though there are also differences that reflect changes in developmental processes. Conclusions The brittle star expresses genes representing all functional classes at the gastrula stage. Brittle stars and sea urchins have comparable numbers of each class of genes and share many of the genes expressed at gastrulation. Examination of the brittle star genes in which sea urchin orthologs are utilized in germ layer specification reveals a relatively higher level of conservation of key regulatory components compared to the overall transcriptome. We also identify genes that were either lost or whose temporal expression has diverged from that of sea urchins

The North West Redwater Sturgeon Refinery: What are the Numbers for Alberta’s Investment?

Since 2006, the government of Alberta has tried to increase the volume of raw bitumen upgraded and refined in the province. More specifically, the Alberta Petroleum Marketing Commission (APMC) and Canadian Natural Resources Ltd. (CNRL) have entered into agreements with a facility northeast of Edmonton called the North West Redwater (NWR) Sturgeon Refinery. The NWR Sturgeon Refinery is designed to process 79,000 barrels per day (bpd) of feedstock, consisting of 50,000 bpd of bitumen and 29,000 bpd of diluent (referred to as dilbit). The refinery will produce petroleum products consisting of approximately 40,000 bpd of low sulphur diesel, 28,000 bpd of diluent and 13,000 bpd of other lighter petroleum products. It will also be able to capture 1.2 million tonnes per year of carbon dioxide emitted from the refinery’s operations. This captured carbon dioxide will be compressed, put into a pipeline and then injected into an existing oil field in order to achieve increased production of crude oil (referred to as enhanced oil recovery or EOR). It is the first refinery built in Canada since 1984, and the first one in Canada to refine bitumen into petroleum products such as diesel fuel. It differs from the upgrader built in Lloydminster which only upgrades bitumen into synthetic crude oil that requires further refining at a conventional refinery in order to produce petroleum products. This paper gives a description of the structure of this support by APMC and CNRL using a mechanism whereby those two parties agree to enter into tolling agreements to process the diluted bitumen feedstock into refined petroleum products for sale. Under the tolling agreement, APMC and CNRL retain ownership of the diluted bitumen as it is refined into petroleum products. APMC and CNRL then sell such petroleum products, and pay a tolling fee to the NWR Sturgeon Refinery for the refining service provided. The paper also uses an economic model in Excel to give a projection of the economics of this facility for the first full year of operation. The objective is to put numbers to a project that has been the subject of much qualitative discussion. The Excel economic model contains base case assumptions for a number of variables such as the capital cost of the refinery, the financing costs associated with such capital costs, the operating costs of the refinery, the cost of the diluted bitumen feedstock and the price of the petroleum products produced by and sold from the refinery. Based on these base case assumptions, the Excel economic model shows that in the first full year of operation of the NWR Sturgeon Refinery in 2019, the two toll-paying entities, APMC and CNRL, are projected to lose a cash amount of about $24 million (about$1 per barrel of diluted bitumen supplied). This loss is based on a comparison to the toll payers’ alternative of just selling the diluted bitumen feedstock at market prices. The paper then uses the economic model to do a sensitivity analysis to show the effect of a lower or higher price of diluted bitumen feedstock, as well as the effect of a lower or higher price of the produced petroleum products. If the cost of the diluted bitumen feedstock were lower, or the price of the petroleum products were higher, then APMC and CNRL would earn a profit. If the converse occurred (feedstock costs higher or petroleum product price lower), then the loss to APMC and CNRL would be greater than $24 million. Finally, the paper attempts to create a template for governments to use when they consider whether or not to provide financial assistance to various projects

An evaluation of intensive care severity of illness scoring models

Objectives: To evaluate the accuracy of the four main Intensive Care severity of illness scoring models using a large Scottish database, and to investigate different strategies for improving their accuracy in a Scottish setting.Method: Twenty two out of 25 general adult Intensive Care Units in Scotland collected data for two and half years to allow calculation of Acute Physiology and Chronic Health Evaluation (APACHE) version II and III, Simplified Acute Physiology Score (SAPS) version II, Mortality Probability Model (MPM) version II (calculated on admission and at 24 hours). The models' Goodness of Fit (discrimination and calibration) and performances in subgroups (Uniformity of Fit) were evaluated using Receiver Operating Characteristic Curves, Hosmer-Lemeshow Goodness of Fit test, Chi Squared test and Confidence Intervals. Three of the Models (APACHE II, SAPS II, and MPM II) were customised with Scottish data using logistic regression techniques.Results: All models had good discrimination but poor calibration. However, the SAPS II and APACHE II models appeared to have better calibration than other models.All models, except the new APACHE II model, showed significant differences in important subgroups.Conclusions: Questions remain about the accuracy of these models even after customisation. Further research is needed to investigate variations in Intensive Care Units and the relationship to clinical effectiveness. However, where case mix adjustment is needed the new customised models remain the most accurate means of doing this in Scottish dat

Microwave Components with MEMS Switches

RF MEMS switches with metal-metal contacts are being developed for microwave applications where broadband, high linearity performance is required. These switches provide less than 0.2 dB insertion loss through 40 GHz. This paper describes the integration of these switches into selected microwave components such as reconfigurable antenna elements, tunable filters, switched delay lines, and SPDT switches. Microwave and millimeter wave measured results from these circuits are presented

The Grizzly, October 30, 1990

Ursinus Honored at Governor\u27s Mansion • Sam Stretton To Speak • Glassmoyer Retires • Heefner New Board President • The Gender of Speech: A Tri-Lambda Lecture • Career Day November 6th • Forbes to Speak to Clergy • Animal Lovers Unite • Mock DWI A Hit • Student Camp Experience • David is Great!! • Presenting Protheatre: The Changeling • Crutcher Leads Team• Muhlenberg Falls • Swimmers Open Season at Relay Meet • Women Running To MAC\u27s • Men Go for MAC Title • Soccer • Letters: Keep Ursinus Clean; Quad Keys Revoked?; Signs Stolen; Security, Please Hold • Environmentally Concerned? Get Active • Bush\u27s Environmental Lip Service • This Time for Real • Nature Versus Nurture: A Step in Solving the Puzzlehttps://digitalcommons.ursinus.edu/grizzlynews/1262/thumbnail.jp

Genetic Diversity of Near Genome-Wide Hepatitis C Virus Sequences during Chronic Infection: Evidence for Protein Structural Conservation Over Time

Infection with hepatitis C virus (HCV) is one of the leading causes of chronic hepatitis, liver cirrhosis and end-stage liver disease worldwide. The genetics of HCV infection in humans and the disease course of chronic hepatitis C are both remarkably variable. Although the response to interferon treatment is largely dependent on HCV genotypes, whether or not a relationship exists between HCV genome variability and clinical course of hepatitis C disease still remains unknown. To more thoroughly understand HCV genome evolution over time in association with disease course, near genome-wide HCV genomes present in 9 chronically infected participants over 83 total study years were sequenced. Overall, within HCV genomes, the number of synonymous substitutions per synonymous site (dS) significantly exceeded the number of non-synonymous substitutions per site (dN). Although both dS and dN significantly increased with duration of chronic infection, there was a highly significant decrease in dN/dS ratio in HCV genomes over time. These results indicate that purifying selection acted to conserve viral protein structure despite persistence of high level of nucleotide mutagenesis inherent to HCV replication. Based on liver biopsy fibrosis scores, HCV genomes from participants with advanced fibrosis had significantly greater dS values and lower dN/dS ratios compared to participants with mild liver disease. Over time, viral genomes from participants with mild disease had significantly greater annual changes in dN, along with higher dN/dS ratios, compared to participants with advanced fibrosis. Yearly amino acid variations in the HCV p7, NS2, NS3 and NS5B genes were all significantly lower in participants with severe versus mild disease, suggesting possible pathogenic importance of protein structural conservation for these viral gene products

Pregnancy outcomes related to the treatment of sarcomas with anthracyclines and/or ifosfamide during pregnancy

BACKGROUND: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas. PATIENTS AND METHODS: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples. RESULTS: We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and nine soft tissue sarcomas diagnosed at a mean gestational age of 16.7 ± 5.9 weeks. Only nine patients had live births (9/13, 69.2%), with mean gestational age of 30.8 ± 3.8 weeks at delivery. The four patients with pregnancy loss all received both doxorubicin and ifosfamide, with chemotherapy initiated at 15.5 weeks as compared with 21.3 weeks for those patients with live births (p = 0.016). CONCLUSION: In this multi-institutional study of sarcoma chemotherapy regimens administered during pregnancy, we found a high rate of fetal demise that was seen only in patients receiving both doxorubicin and ifosfamide and statistically more likely with chemotherapy initiation earlier in the second trimester. While limited by a small sample size, our study represents the largest study of sarcoma patients that received anthracyclines and/or ifosfamide in pregnancy thus far reported and supports development of an international registry to study concerns raised by our study

Metabolic compensation activates pro-survival mTORC1 signaling upon 3-phosphoglycerate dehydrogenase inhibition in osteosarcoma

Osteosarcoma is the most common pediatric and adult primary malignant bone cancer. Curative regimens target the folate pathway, downstream of serine metabolism, with high-dose methotrexate. Here, the rate-limiting enzyme in the biosynthesis of serine from glucose, 3-phosphoglycerate dehydrogenase (PHGDH), is examined, and an inverse correlation between PHGDH expression and relapse-free and overall survival in osteosarcoma patients is found. PHGDH inhibition in osteosarcoma cell lines attenuated cellular proliferation without causing cell death, prompting a robust metabolic analysis to characterize pro-survival compensation. Using metabolomic and lipidomic profiling, cellular response to PHGDH inhibition is identified as accumulation of unsaturated lipids, branched chain amino acids, and methionine cycle intermediates, leading to activation of pro-survival mammalian target of rapamycin complex 1 (mTORC1) signaling. Increased mTORC1 activation sensitizes cells to mTORC1 pathway inhibition, resulting in significant, synergistic cell death in vitro and in vivo. Identifying a therapeutic combination for PHGDH-high cancers offers preclinical justification for a dual metabolism-based combination therapy for osteosarcoma