The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histological progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neo-angiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution towards an IDHwt-like phenotype

Trends and risk factors for human Q fever in Australia, 1991-2014

Australian abattoir workers, farmers, veterinarians and people handling animal birthing products or slaughtering animals continue to be at high risk of Q fever despite an effective vaccine being available. National Notifiable Diseases Surveillance System data were analysed for the period 1991-2014, along with enhanced risk factor data from notified cases in the states of New South Wales and Queensland, to examine changes in the epidemiology of Q fever in Australia. The national Q fever notification rate reduced by 20% [ incident rate ratio (IRR) 0.82] following the end of the National Q fever Management Program in 2006, and has increased since 2009 (IRR 1.01-1.34). Highest rates were in males aged 40-59 years (5.9/ 100 000) and 87% of Q fever cases occurred in New South Wales and Queensland. The age of Q fever cases and proportion of females increased over the study period. Based on the enhanced risk factor data, the most frequently listed occupation for Q fever cases involved contact with livestock, followed by ` no known risk' occupations. More complete and comparable enhanced risk factor data, at the State/ Territory and national levels, would aid in further understanding of the epidemiology of Q fever

Future research directions on the “Elusive” White Shark

White sharks, Carcharodon carcharias, are often described as elusive, with little information available due to the logistical difficulties of studying large marine predators that make long-distance migrations across ocean basins. Increased understanding of aggregation patterns, combined with recent advances in technology have, however, facilitated a new breadth of studies revealing fresh insights into the biology and ecology of white sharks. Although we may no longer be able to refer to the white shark as a little-known, elusive species, there remain numerous key questions that warrant investigation and research focus. Although white sharks have separate populations, they seemingly share similar biological and ecological traits across their global distribution. Yet, white shark’s behavior and migratory patterns can widely differ, which makes formalizing similarities across its distribution challenging. Prioritization of research questions is important to maximize limited resources because white sharks are naturally low in abundance and play important regulatory roles in the ecosystem. Here, we consulted 43 white shark experts to identify these issues. The questions listed and developed here provide a global road map for future research on white sharks to advance progress toward key goals that are informed by the needs of the research community and resource managers

Transcription and translation of phloem protein (PP2) during phloem differentiation in Cucurbita maxima

The synthesis of a major phloem protein, PP2, was investigated by measurement of the mRNA at various stages of phloem development in Cucurbita. Quantitative assays with immuno-electrophoresis showed that the amounts of PP2 in hypocotyls of Cucurbita seedlings increased with the age of seedlings. An increase in mRNA for PP2 during the early stages of seedling growth was also observed by immunoprecipitation of the invitro translation products of hypocotyl polyadenylated RNA. There was close timing in the variations of PP2 synthesised in vivo and in the changes in amounts of translatable PP2-mRNA during the course of seedling growth. A complementary-DNA (cDNA) library to polyadenylated RNA from hypocotyls of 3-d-old Cucurbita seedlings has been constructed. Two cDNA clones, A and B, have been identified by hybrid-release translation to be complementary to the mRNA coding for PP2. The levels of total mRNA for PP2 measured with clone A were found to increase in the first 4 d of seedling growth but decreased to lower levels in older seedlings. Regulatory controls on both transcription and modification of transcripts appeared to occur during the synthesis of PP2. © 1987 Springer-Verlag.link_to_subscribed_fulltex