Effects of macroalgal removal on inshore coral reef communities and sedimentation dynamics

Stella Fulton investigated the impact of removing macroalgae from degraded inshore reefs around Magnetic Island. She found that periodically removing macroalgae over three years led to significantly higher coral cover and reduced re-growth of macroalgae. Macroalgal removal may therefore be an effective strategy to assist coral recovery on degraded reefs

Catholic belief and survival in late sixteenth-century Vienna : the case of Georg Eder (1523-1587)

This thesis is a detailed study of the religious belief and survival of one of the most prominent figures of late sixteenth-century Vienna, Georg Eder (1523- 1587). Eder held a number of high positions at Vienna University and the city's Habsburg court between 1552 and 1584, but his increasingly uncompromising Catholicism placed him at odds with many influential figures around him, not least the confessionally moderate Habsburg Emperor Maximilian II. Pivoted around an incident in 1573, when Eder's ferocious polemic, Evangelische Inquisition, fell under Imperial condemnation, the thesis investigates three key aspects of Eder's life. It examines Eder's position as a Catholic in the Vienna of his day; the public expression of this Catholicism and the strong Jesuit influence on the same; and Eder's rescue and subsequent survival as a lay advocate of Catholic reform, largely through the protection of the Habsburgs' rivals, the Wittelsbach Dukes of Bavaria. Based on a wide variety of printed and manuscript material, this thesis contributes to existing historiography on two levels. On one, it is a reconstruction of the career of one of Vienna's most prominent yet under-studied figures, in a period when the city itself was one of Europe's most politically and religiously significant. In a broader sense, however, this study also adds to the wider canon of Reformation history. It re-examines the nature and extent of Catholicism at the Viermese court in the latter half of the sixteenth century. It highlights the growing role of Eder's Wittelsbach patrons as defenders of Catholicism, even beyond their own Bavarian borders. The thesis also emphasises the role, potential and realised, of influential laity such as Eder in advancing the cause of Catholic reform in the late sixteenth century. Thus it is a strong challenge to the existing, prevalent portrayal of the sixteenth-century Catholic laity as an anonymous and largely passive group who merely responded to the ministries of others

Resistance-promoting effects of ependymoma treatment revealed through genomic analysis of multiple recurrences in a single patient

As in other brain tumors, multiple recurrences after complete resection and irradiation of supratentorial ependymoma are common and frequently result in patient death. This standard-of-care treatment was established in the pregenomic era without the ability to evaluate the effect that mutagenic therapies may exert on tumor evolution and in promoting resistance, recurrence, and death. We seized a rare opportunity to characterize treatment effects and the evolution of a single patient's ependymoma across four recurrences after different therapies. A combination of high-depth whole-genome and exome-based DNA sequencing of germline and tumor specimens, RNA sequencing of tumor specimens, and advanced computational analyses were used. Treatment with radiation and chemotherapies resulted in a substantial increase in mutational burden and diversification of the tumor subclonal architecture without eradication of the founding clone. Notable somatic alterations included a MEN1 driver, several epigenetic modifiers, and therapy-induced mutations that impacted multiple other cancer-relevant pathways and altered the neoantigen landscape. These genomic data provided new mechanistic insights into the genesis of ependymoma and pathways of resistance. They also revealed that radiation and chemotherapy were significant forces in shaping the increased subclonal complexity of each tumor recurrence while also failing to eradicate the founding clone. This raises the question of whether standard-of-care treatments have similar consequences in other patients with ependymoma and other types of brain tumors. If so, the perspective obtained by real-time genomic characterization of a tumor may be essential for making effective patient-specific and adaptive clinical decisions.</jats:p

A novel retinoblastoma therapy from genomic and epigenetic analyses.

Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss

Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma

Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype. To identify these potential cooperating genetic mutations, we performed whole-genome sequencing (WGS) analysis of three NF1-associated pilocytic astrocytoma (PA) tumors. We found that the mechanism of somatic NF1 loss was different in each tumor (frameshift mutation, loss of heterozygosity, and methylation). In addition, tumor purity analysis revealed that these tumors had a high proportion of stromal cells, such that only 50%–60% of cells in the tumor mass exhibited somatic NF1 loss. Importantly, we identified no additional recurrent pathogenic somatic mutations, supporting a model in which neuroglial progenitor cell NF1 loss is likely sufficient for PA formation in cooperation with a proper stromal environment