Repositioning Brusatol as a Transmission Blocker of Malaria Parasites.

Currently, primaquine is the only malaria transmission-blocking drug recommended by the WHO. Recent efforts have highlighted the importance of discovering new agents that regulate malarial transmission, with particular interest in agents that can be administered in a single low dose, ideally with a discrete and Plasmodium-selective mechanism of action. Here, our team demonstrates an approach to identify malaria transmission-blocking agents through a combination of in vitro screening and in vivo analyses. Using a panel of natural products, our approach identified potent transmission blockers, as illustrated by the discovery of the transmission-blocking efficacy of brusatol. As a member of a large family of biologically active natural products, this discovery provides a critical next step toward developing methods to rapidly identify quassinoids and related agents with valuable pharmacological therapeutic properties.

FicD regulates adaptation to the unfolded protein response in the murine liver.

The unfolded protein response (UPR) is a cellular stress response that is activated when misfolded proteins accumulate in the endoplasmic reticulum (ER). Regulation of the UPR response must be adapted to the needs of the cell as prolonged UPR responses can result in disrupted cellular function and tissue damage. Previously, we discovered that the enzyme FicD (also known as Fic or HYPE) through its AMPylation and deAMPylation activity can modulate the UPR response via post-translational modification of BiP. FicD AMPylates BiP during homeostasis and deAMPylates BiP during stress. We hypothesized that FicD regulation of the UPR will play a role in mitigating the deleterious effects of UPR activation in tissues with frequent physiological stress. Here, we explore the role of FicD in the murine liver. As seen in our pancreatic studies, livers lacking FicD exhibit enhanced UPR signaling in response to short term physiologic fasting and feeding stress. However, in contrast to studies on the pancreas, livers, as a more regenerative tissue, remained remarkably resilient in the absence of FicD. The livers of FicD-/- did not show marked changes in UPR signaling or damage after either chronic high fat diet (HFD) feeding or acute pathological UPR induction. Intriguingly, FicD-/- mice showed changes in UPR induction and weight loss patterns following repeated pathological UPR induction. These findings indicate that FicD regulates UPR responses during mild physiological stress and in adaptation to repeated stresses, but there are tissue specific differences in the requirement for FicD regulation.

FicD regulates adaptation to the unfolded protein response in the murine liver.

The unfolded protein response (UPR) is a cellular stress response that is activated when misfolded proteins accumulate in the endoplasmic reticulum (ER). The UPR elicits a signaling cascade that results in an upregulation of protein folding machinery and cell survival signals. However, prolonged UPR responses can result in elevated cellular inflammation, damage, and even cell death. Thus, regulation of the UPR response must be tuned to the needs of the cell, sensitive enough to respond to the stress but pliable enough to be stopped after the crisis has passed. Previously, we discovered that the bi-functional enzyme FicD can modulate the UPR response via post-translational modification of BiP. FicD AMPylates BiP during homeostasis and deAMPylates BiP during stress. We found this activity is important for the physiological regulation of the exocrine pancreas. Here, we explore the role of FicD in the murine liver. Like our previous studies, livers lacking FicD exhibit enhanced UPR signaling in response to short term physiologic fasting and feeding stress. However, the livers of FicD -/- did not show marked changes in UPR signaling or damage after either chronic high fat diet (HFD) feeding or acute pathological UPR induction. Intriguingly, FicD -/- mice showed changes in UPR induction and weight loss patterns following repeated pathological UPR induction. These findings show that FicD regulates UPR responses during mild physiological stress and may play a role in maintaining resiliency of tissue through adaptation to repeated ER stress.

Community-science reveals delayed fall migration of waterfowl and spatiotemporal effects of a changing climate.

Climate change has well-documented, yet variable, influences on the annual movements of migratory birds. The effects of climate change on fall migration remains understudied compared with spring but appears to be less consistent among species, regions and years. Changes in the pattern and timing of waterfowl migration in particular may result in cascading effects on ecosystem function, and socio-economic and cultural outcomes. We investigated changes in the migration of 15 waterfowl species along a major flyway corridor of continental importance in northeastern North America using 43 years of community-science data. We built spatially- and temporally explicit hierarchical generative additive models for each species and demonstrated that climate, specifically the interaction between minimum temperature and precipitation, significantly influences migration phenology for most species. Certain species' migratory movements responded to specific temperature thresholds (climate migrants) and others reacted more to the interaction of temperature and precipitation (extreme event migrants). There are already significant changes in the fall migration phenology of common waterfowl species with high ecological and economic importance, which may simply increase in the context of a changing climate. If not addressed, climate change could induce mismatches in management, regulations and population surveys which would negatively impact the hunting industry. Our findings highlight the importance of considering species-specific spatiotemporal scales of effect on climate on migration and our methods can be widely adapted to quantify and forecast climate-driven changes in wildlife migration.

Les changements climatiques ont des influences bien documentées, mais variables, sur les mouvements annuels des oiseaux migrateurs. Les effets des changements climatiques sur les migrations automnales demeurent peu étudiés par rapport aux migrations printanières, mais il semble qu'ils soient moins constants d'une espèce, d'une région et d'une année à l'autre. Les changements dans le patron et le calendrier de la migration de la sauvagine en particulier peuvent avoir des effets en chaîne sur la fonction des écosystèmes et des impacts socio­économiques et culturels. Nous avons étudié les changements dans la migration de 15 espèces de sauvagine le long d'un corridor de migration d'importance continentale dans le nord­est de l'Amérique du Nord, en utilisant 43 ans de données scientifiques communautaires. Nous avons construit des modèles additifs généralisés hiérarchiques spatialement et temporellement explicites pour chaque espèce et avons démontré que le climat, en particulier l'interaction entre la température minimale et les précipitations, influence de manière significative la phénologie de la migration pour la plupart des espèces. Les mouvements migratoires de certaines espèces répondent à des seuils de température spécifiques (migrateurs climatiques) et d'autres réagissent davantage à l'interaction entre la température et les précipitations (migrateurs d'événements extrêmes). La phénologie des migrations automnales d'espèces de sauvagine commune qui ont une grande importance écologique et économique connaît déjà des changements importants, qui pourraient simplement s'accentuer dans le cadre des changements climatiques. S'ils ne sont pas pris en compte, les changements climatiques pourraient induire des décalages dans la gestion, les réglementations et les enquêtes de population, ce qui aurait un impact négatif sur l'industrie de la chasse. Nos résultats soulignent l'importance de prendre en compte les échelles spatio­temporelles spécifiques sur la migration et nos méthodes peuvent être largement adaptées pour quantifier et prévoir les changements induits par le climat dans la migration de la faune.

Population decline in tree swallows (Tachycineta bicolor) linked to climate change and inclement weather on the breeding ground.

Population decline and the threat of extinction are realities currently facing many species. Yet, in most cases, the detailed demographic data necessary to identify causes of population decline are unavailable. Using 43 years (1975-2017) of data from a box-nesting population of tree swallows (Tachycineta bicolor), we identified reduced survival of offspring as a probable demographic cause of population decline. Poor fledging success was associated with increased predation and poor weather conditions during early nestling development. Low juvenile survival and subsequent recruitment was linked to poor weather conditions during the post-fledging period and may also be linked to conditions on the wintering grounds. Regional weather conditions during critical stages of breeding (early nestling and post-fledging) have become progressively worse over the 43-year study period. None of the other factors linked to offspring survival have similarly deteriorated. Overall, our results suggest tree swallows should be added to the growing list of species challenged by climate change, and that other species of aerial insect specialists may face similar impacts of climate change.

The cases for and against double-blind reviews.

To date, the majority of authors on scientific publications have been men. While much of this gender bias can be explained by historic sexism and discrimination, there is concern that women may still be disadvantaged by the peer review process if reviewers' biases lead them to reject publications with female authors more often. One potential solution to this perceived gender bias in the reviewing process is for journals to adopt double-blind reviews whereby neither the authors nor the reviewers are aware of each other's identity and gender. To test the efficacy of double-blind reviews in one behavioral ecology journal (Behavioral Ecology, BE), we assigned gender to every authorship of every paper published for 2010-2018 in that journal compared to four other journals with single-blind reviews but similar subject matter and impact factors. While female authorships comprised only 35% of the total in all journals, the double-blind journal (BE) did not have more female authorships than its single-blind counterparts. Interestingly, the incidence of female authorship is higher at behavioral ecology journals (BE and Behavioral Ecology and Sociobiology) than in the ornithology journals (Auk, Condor, Ibis) for papers on all topics as well as those on birds. These analyses suggest that double-blind review does not currently increase the incidence of female authorship in the journals studied here. We conclude, at least for these journals, that double-blind review no longer benefits female authors and we discuss the pros and cons of the double-blind reviewing process based on our findings.

Rainy springs linked to poor nestling growth in a declining avian aerial insectivore ( Tachycineta bicolor).

As species shift their ranges and phenology to cope with climate change, many are left without a ready supply of their preferred food source during critical life stages. Food shortages are often assumed to be driven by reduced total food abundance, but here we propose that climate change may cause short-term food shortages for foraging specialists without affecting overall food availability. We frame this hypothesis around the special case of birds that forage on flying insects for whom effects mediated by their shared food resource have been proposed to cause avian aerial insectivores' decline worldwide. Flying insects are inactive during cold, wet or windy conditions, effectively reducing food availability to zero even if insect abundance remains otherwise unchanged. Using long-term monitoring data from a declining population of tree swallows ( Tachycineta bicolor), we show that nestlings' body mass declined substantially from 1977 to 2017. In 2017, nestlings had lower body mass if it rained during the preceding 3 days, though females increased provisioning rates, potentially in an attempt to compensate. Adult body mass, particularly that of the males, has also declined over the long-term study. Mean rainfall during the nestling period has increased by 9.3 ± 0.3 mm decade-1, potentially explaining declining nestling body mass and population declines. Therefore, we suggest that reduced food availability, distinct from food abundance, may be an important and previously overlooked consequence of climate change, which could be affecting populations of species that specialize on foraging on flying insects.