Drosophila melanogaster Set8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation.

Monomethylation of lysine 20 of histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects of genome function that are mediated by H4K20me binding proteins. We interrogated this model in a developing animal by comparing in parallel the transcriptomes of Set8 null, H4 K20R/A, and l(3)mbt mutant Drosophila melanogaster. We found that the gene expression profiles of H4 K20A and H4 K20R larvae are markedly different than Set8 null larvae despite similar reductions in H4K20me1. Set8 null mutant cells have a severely disrupted transcriptome and fail to proliferate in vivo, but these phenotypes are not recapitulated by mutation of H4 K20, indicating that the developmental defects of Set8 null animals are largely due to H4K20me1-independent effects on gene expression. Furthermore, the H4K20me1 binding protein L(3)mbt is recruited to the transcription start sites of most genes independently of H4K20me even though genes bound by L(3)mbt have high levels of H4K20me1. Moreover, both Set8 and L(3)mbt bind to purified H4K20R nucleosomes in vitro. We conclude that gene expression changes in Set8 null and H4 K20 mutants cannot be explained by loss of H4K20me1 or L(3)mbt binding to chromatin and therefore that H4K20me1 does not play a large role in gene expression

Ocean acidification disrupts the orientation of postlarval Caribbean spiny lobsters

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gravinese, P. M., Page, H. N., Butler, C. B., Spadaro, A. J., Hewett, C., Considine, M., Lankes, D., & Fisher, S. Ocean acidification disrupts the orientation of postlarval Caribbean spiny lobsters. Scientific Reports, 10(1), (2020): 18092, doi:10.1038/s41598-020-75021-9.Anthropogenic inputs into coastal ecosystems are causing more frequent environmental fluctuations and reducing seawater pH. One such ecosystem is Florida Bay, an important nursery for the Caribbean spiny lobster, Panulirus argus. Although adult crustaceans are often resilient to reduced seawater pH, earlier ontogenetic stages can be physiologically limited in their tolerance to ocean acidification on shorter time scales. We used a Y-maze chamber to test whether reduced-pH seawater altered the orientation of spiny lobster pueruli toward chemical cues produced by Laurencia spp. macroalgae, a known settlement cue for the species. We tested the hypothesis that pueruli conditioned in reduced-pH seawater would be less responsive to Laurencia spp. chemical cues than pueruli in ambient-pH seawater by comparing the proportion of individuals that moved to the cue side of the chamber with the proportion that moved to the side with no cue. We also recorded the amount of time (sec) before a response was observed. Pueruli conditioned in reduced-pH seawater were less responsive and failed to select the Laurencia cue. Our results suggest that episodic acidification of coastal waters might limit the ability of pueruli to locate settlement habitats, increasing postsettlement mortality.We thank the Steinwachs Family Foundation, which provided funding that supported Gravinese’s postdoctoral fellowship at Mote Marine Laboratory and Aquarium. We also acknowledge the partial support provided by the St. Petersburg College Titan Achievement minigrant program. Page was supported by a Mote Marine Laboratory and Aquarium Postdoctoral Research Fellowship. Postlarval spiny lobsters were collected with a state-issued Special Activity License (SAL-17-1868G-SR). We also thank those who helped with animal collection throughout this work including in-kind support provided by E. Muller and the Mote CAOS facility, as well as E. Bartels and C. Walter of the Coral Reef Monitoring and Assessment Program at Mote Marine Laboratory and Aquarium, as well as other field personnel including: L. Toth, S. Perry, T. Parker, A. Fine, L. Humphrey, and many undergraduate interns. We also thank L. Toth, E. Ross, B. Sharp, C. Crowley, J. Butler, and B. Crowder for editorial comments

Non-compliance and under-performance in Australian human-induced regeneration projects

The ‘boom-and-bust’ nature of rangelands makes them ill-suited to nature-based solutions (NbS) involving carbon sequestration in vegetation and soils. The variability in these ecosystems makes it difficult to determine whether carbon stock changes are attributable to project activities, creating additionality risks. Low and variable rainfall also means carbon stock increases will often be impermanent, being susceptible to reversals in droughts, a risk magnified by climate change. The small potential for gains per unit area over vast regions makes it difficult to accurately measure carbon stock changes at low cost. This creates pressure to trade accuracy for simplicity in measurement approaches, increasing the risk of errors. Despite these risks, rangelands have been advanced as suitable for offset projects because of low opportunity cost and a perception they are extensively degraded. The most prominent example globally is human-induced regeneration (HIR) projects under the Australian carbon credit unit (ACCU) scheme, which are purporting to regenerate permanent even-aged native forests (≥20% canopy cover from trees ≥2 metres high) across millions of hectares of largely uncleared rangelands, predominantly by reducing grazing pressure. Previous research found limited forest regeneration in the credited areas of these projects, and that most of the observed changes in tree cover were attributable to factors other than the project activities. Here we extend this research by evaluating compliance of a sample of 116 HIR projects with regulatory requirements and their performance in increasing sequestration in regeneration. The results suggest most HIR projects are non-compliant with key regulatory requirements that are essential to project integrity, and have had minimal impact on woody vegetation cover in credited areas. The findings point to major administrative and governance failings in Australia’s carbon credit scheme, and a significant missed opportunity to restore biodiversity-rich woodlands and forests in previously cleared lands via legitimate carbon offset projects

Deep Sequencing of the Nicastrin Gene in Pooled DNA, the Identification of Genetic Variants That Affect Risk of Alzheimer's Disease

Nicastrin is an obligatory component of the γ-secretase; the enzyme complex that leads to the production of Aβ fragments critically central to the pathogenesis of Alzheimer's disease (AD). Analyses of the effects of common variation in this gene on risk for late onset AD have been inconclusive. We investigated the effect of rare variation in the coding regions of the Nicastrin gene in a cohort of AD patients and matched controls using an innovative pooling approach and next generation sequencing. Five SNPs were identified and validated by individual genotyping from 311 cases and 360 controls. Association analysis identified a non-synonymous rare SNP (N417Y) with a statistically higher frequency in cases compared to controls in the Greek population (OR 3.994, CI 1.105–14.439, p = 0.035). This finding warrants further investigation in a larger cohort and adds weight to the hypothesis that rare variation explains some of genetic heritability still to be identified in Alzheimer's disease

Elite Suppressors Harbor Low Levels of Integrated HIV DNA and High Levels of 2-LTR Circular HIV DNA Compared to HIV+ Patients On and Off HAART

Elite suppressors (ES) are a rare population of HIV-infected individuals that are capable of naturally controlling the infection without the use of highly active anti-retroviral therapy (HAART). Patients on HAART often achieve viral control to similar (undetectable) levels. Accurate and sensitive methods to measure viral burden are needed to elucidate important differences between these two patient populations in order to better understand their mechanisms of control. Viral burden quantification in ES patients has been limited to measurements of total DNA in PBMC, and estimates of Infectious Units per Million cells (IUPM). There appears to be no significant difference in the level of total HIV DNA between cells from ES patients and patients on HAART. However, recovering infectious virus from ES patient samples is much more difficult, suggesting their reservoir size should be much smaller than that in patients on HAART. Here we find that there is a significant difference in the level of integrated HIV DNA in ES patients compared to patients on HAART, providing an explanation for the previous results. When comparing the level of total to integrated HIV DNA in these samples we find ES patients have large excesses of unintegrated HIV DNA. To determine the composition of unintegrated HIV DNA in these samples, we measured circular 2-LTR HIV DNA forms and found ES patients frequently have high levels of 2-LTR circles in PBMC. We further show that these high levels of 2-LTR circles are not the result of inefficient integration in ES cells, since HIV integrates with similar efficiency in ES and normal donor cells. Our findings suggest that measuring integration provides a better surrogate of viral burden than total HIV DNA in ES patients. Moreover, they add significantly to our understanding of the mechanisms that allow viral control and reservoir maintenance in this unique patient population

Identifying educator behaviours for high quality verbal feedback in health professions education: literature review and expert refinement

Background Health professions education is characterised by work-based learning and relies on effective verbal feedback. However the literature reports problems in feedback practice, including lack of both learner engagement and explicit strategies for improving performance. It is not clear what constitutes high quality, learner-centred feedback or how educators can promote it. We hoped to enhance feedback in clinical practice by distinguishing the elements of an educator’s role in feedback considered to influence learner outcomes, then develop descriptions of observable educator behaviours that exemplify them. Methods An extensive literature review was conducted to identify i) information substantiating specific components of an educator’s role in feedback asserted to have an important influence on learner outcomes and ii) verbal feedback instruments in health professions education, that may describe important educator activities in effective feedback. This information was used to construct a list of elements thought to be important in effective feedback. Based on these elements, descriptions of observable educator behaviours that represent effective feedback were developed and refined during three rounds of a Delphi process and a face-to-face meeting with experts across the health professions and education. Results The review identified more than 170 relevant articles (involving health professions, education, psychology and business literature) and ten verbal feedback instruments in health professions education (plus modified versions). Eighteen distinct elements of an educator’s role in effective feedback were delineated. Twenty five descriptions of educator behaviours that align with the elements were ratified by the expert panel. Conclusions This research clarifies the distinct elements of an educator’s role in feedback considered to enhance learner outcomes. The corresponding set of observable educator behaviours aim to describe how an educator could engage, motivate and enable a learner to improve. This creates the foundation for developing a method to systematically evaluate the impact of verbal feedback on learner performance

Journalism as usual: The use of social media as a newsgathering tool in the coverage of the Iranian elections in 2009

The Iranian elections of June 2009 and the ensuing protests were hailed as the 'Twitter revolution' in the media in the United Kingdom. However, this study of the use of sources by journalists covering the events shows that despite their rhetoric of the importance of social media in alerting the global community to events in Iran, journalists themselves did not turn to that social media for their own information, but relied most on traditional sourcing practices: political statements, expert opinion and a handful of 'man on the street' quotes for colour. This study shows that although the mythology of the Internet as a place where all voices are equal, and have equal access to the public discourse continues – a kind of idealized 'public sphere' – the sourcing practices of journalists and the traditions of coverage continue to ensure that traditional voices and sources are heard above the crowd