HP1 Recruits Activity-Dependent Neuroprotective Protein to H3K9me3 Marked Pericentromeric Heterochromatin for Silencing of Major Satellite Repeats

H3 lysine 9 trimethylation (H3K9me3) is a histone posttranslational modification (PTM) that has emerged as hallmark of pericentromeric heterochromatin. This constitutive chromatin domain is composed of repetitive DNA elements, whose transcription is differentially regulated. Mammalian cells contain three HP1 proteins, HP1α, HP1β and HP1γ These have been shown to bind to H3K9me3 and are thought to mediate the effects of this histone PTM. However, the mechanisms of HP1 chromatin regulation and the exact functional role at pericentromeric heterochromatin are still unclear. Here, we identify activity-dependent neuroprotective protein (ADNP) as an H3K9me3 associated factor. We show that ADNP does not bind H3K9me3 directly, but that interaction is mediated by all three HP1 isoforms in vitro. However, in cells ADNP localization to areas of pericentromeric heterochromatin is only dependent on HP1α and HP1β. Besides a PGVLL sequence patch we uncovered an ARKS motif within the ADNP homeodomain involved in HP1 dependent H3K9me3 association and localization to pericentromeric heterochromatin. While knockdown of ADNP had no effect on HP1 distribution and heterochromatic histone and DNA modifications, we found ADNP silencing major satellite repeats. Our results identify a novel factor in the translation of H3K9me3 at pericentromeric heterochromatin that regulates transcription

Implementing the 2012 North American Waterfowl Management Plan Revision: Populations, Habitat, and People

The North American Waterfowl Management Plan (NAWMP) has established a model for wildlife conservation planning over the last 3 decades. Management at a continental scale, leveraged funding, regional partnerships, and a strong science basis have been notable features. Periodic updates to the NAWMP occurred since implementation in 1986; however, a fundamental revision was accomplished in 2012 after extensive stakeholder engagement. An explicit fundamental goal for waterfowl conservation supporters was added in 2012, complementing existing goals for sustainable populations and sufficient habitat found in previous updates. We present a synopsis of progress toward implementation of the 2012 NAWMP and challenge the waterfowl management community to continue with meaningful steps toward achieving NAWMP goals. Adding goals and objectives for supporters increases potential relevance of NAWMP; however, it also presents a level of complexity that was not entirely anticipated. Additionally, the 2012 NAWMP recognized that traditional support from waterfowl hunters alone will not be sufficient to support waterfowl conservation in the future. Simultaneous consideration of multiple objectives, although implicit before, now is a specific focus for habitat and harvest management affecting hunters and other users of the waterfowl resource. The waterfowl management community is faced with revisiting objectives and management actions related to harvest regulations, landscape priorities, habitat conservation, and public engagement to garner broader support. These persistent management challenges are tangible and relevant candidates for greater integration. Ultimately, the structures and processes supporting waterfowl management also will need to be reconsidered

Constructing treatment episodes from concomitant medication logs: a prospective observational study

ObjectivesTo describe an approach using concomitant medication log records for the construction of treatment episodes. Concomitant medication log records are routinely collected in clinical studies. Unlike prescription and dispensing records, concomitant medication logs collect utilisation data. Logs can provide information about drug safety and drug repurposing.DesignA prospective multicentre, multicohort observational study.SettingTwenty-one clinical sites in the USA, Europe, Israel and Australia.Participants415 subjects from the de novo cohort of the Parkinson’s Progression Markers Initiative.MethodsWe construct treatment episodes of concomitant medication use. The proposed approach treats temporal gaps as a stoppage of medication and temporal overlaps as simultaneous use or changes in dose. Log records with no temporal gaps were combined into a single treatment episode.Results5723 concomitant medication log records were used to construct 3655 treatment episodes for 65 medications. There were 405 temporal gaps representing a stoppage of medication; 985 temporal overlaps representing simultaneous regimens of the same medication and 2696 temporal overlaps representing a change in dose regimen. The median episode duration was 37 months (IQ interval: 11–73 months).ConclusionsThe proposed approach for constructing treatment episodes offers a method of estimating duration and dose of treatment from concomitant medication log records. The accompanying recommendations guide log data collection to improve their quality for drug safety and drug repurposing

Estimating habitat carrying capacity for migrating and wintering waterfowl: Considerations, pitfalls and improvements

Population-based habitat conservation planning for migrating and wintering waterfowl in North America is carried out by habitat Joint Venture (JV) initiatives and is based on the premise that food can limit demography (i.e. food limitation hypothesis). Consequently, planners use bioenergetic models to estimate food (energy) availability and population-level energy demands at appropriate spatial and temporal scales, and translate these values into regional habitat objectives. While simple in principle, there are both empirical and theoretical challenges associated with calculating energy supply and demand including: 1) estimating food availability, 2) estimating the energy content of specific foods, 3) extrapolating site-specific estimates of food availability to landscapes for focal species, 4) applicability of estimates from a single species to other species, 5) estimating resting metabolic rate, 6) estimating cost of daily behaviours, and 7) estimating costs of thermoregulation or tissue synthesis. Most models being used are daily ration models (DRMs) whose set of simplifying assumptions are well established and whose use is widely accepted and feasible given the empirical data available to populate such models. However, DRMs do not link habitat objectives to metrics of ultimate ecological importance such as individual body condition or survival, and largely only consider food-producing habitats. Agent-based models (ABMs) provide a possible alternative for creating more biologically realistic models under some conditions; however, ABMs require different types of empirical inputs, many of which have yet to be estimated for key North American waterfowl. Decisions about how JVs can best proceed with habitat conservation would benefit from the use of sensitivity analyses that could identify the empirical and theoretical uncertainties that have the greatest influence on efforts to estimate habitat carrying capacity. Development of ABMs at restricted, yet biologically relevant spatial scales, followed by comparisons of their outputs to those generated from more simplistic, deterministic models can provide a means of assessing degrees of dissimilarity in how alternative models describe desired landscape conditions for migrating and wintering waterfowl