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"Wright, Timothy"
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A high-throughput phenotypic screen identifies clofazimine as a potential treatment for cryptosporidiosis
Cryptosporidiosis has emerged as a leading cause of non-viral diarrhea in children under five years of age in the developing world, yet the current standard of care to treat Cryptosporidium infections, nitazoxanide, demonstrates limited and immune-dependent efficacy. Given the lack of treatments with universal efficacy, drug discovery efforts against cryptosporidiosis are necessary to find therapeutics more efficacious than the standard of care. To date, cryptosporidiosis drug discovery efforts have been limited to a few targeted mechanisms in the parasite and whole cell phenotypic screens against small, focused collections of compounds. Using a previous screen as a basis, we initiated the largest known drug discovery effort to identify novel anticryptosporidial agents. A high-content imaging assay for inhibitors of Cryptosporidium parvum proliferation within a human intestinal epithelial cell line was miniaturized and automated to enable high-throughput phenotypic screening against a large, diverse library of small molecules. A screen of 78,942 compounds identified 12 anticryptosporidial hits with sub-micromolar activity, including clofazimine, an FDA-approved drug for the treatment of leprosy, which demonstrated potent and selective in vitro activity (EC50 = 15 nM) against C. parvum. Clofazimine also displayed activity against C. hominis-the other most clinically-relevant species of Cryptosporidium. Importantly, clofazimine is known to accumulate within epithelial cells of the small intestine, the primary site of Cryptosporidium infection. In a mouse model of acute cryptosporidiosis, a once daily dosage regimen for three consecutive days or a single high dose resulted in reduction of oocyst shedding below the limit detectable by flow cytometry. Recently, a target product profile (TPP) for an anticryptosporidial compound was proposed by Huston et al. and highlights the need for a short dosing regimen (< 7 days) and formulations for children < 2 years. Clofazimine has a long history of use and has demonstrated a good safety profile for a disease that requires chronic dosing for a period of time ranging 3-36 months. These results, taken with clofazimine's status as an FDA-approved drug with over four decades of use for the treatment of leprosy, support the continued investigation of clofazimine both as a new chemical tool for understanding cryptosporidium biology and a potential new treatment of cryptosporidiosis.
Journal Article
How to get published in the best management journals
Written by top journal editors, this book introduces the publishing process, resolves practical issues, encourages the right methods and gives tips for navigating the review process, understanding journals and publishing across disciplinary boundaries.
Book
Parrots of the Wild
\"Parrots of the Wildis an exhaustive compendium of information about parrots, from their evolutionary history to their behavior to present-day conservation issues. A must-have for anyone interested in these amazing creatures.\" -Irene M. Pepperberg, Professor at Harvard University and author ofAlex & Me: How a Scientist and a Parrot Discovered a Hidden World of Animal Intelligence-and Formed a Deep Bond in the Process\"If you like parrots then you'll love this book. From their evolutionary past to their modern-day love lives,Parrots of the Wildpresents a suitably captivating read. I thought I knew a lot about parrots--until I delved into these pages.\" -Tony Juniper, author ofWhat Has Nature Ever Done for Us?andSpix's Macaw: The Race to Save the World's Rarest Bird
Parrots of the Wildexplores recent scientific discoveries and what they reveal about the lives of wild parrots, which are among the most intelligent and rarest of birds. Catherine A. Toft and Tim Wright discuss the evolutionary history of parrots and how this history affects perceptual and cognitive abilities, diet and foraging patterns, and mating and social behavior. The authors also discuss conservation status and the various ways different populations are adapting to a world that is rapidly changing. The book focuses on general patterns across the 350-odd species of parrots, as well as what can be learned from interesting exceptions to these generalities.A synthetic account of the diversity and ecology of wild parrots, this book distills knowledge from the authors' own research and from their review of more than 2,400 published scientific studies. The book is enhanced by an array of illustrations, including nearly ninety color photos of wild parrots represented in their natural habitats.Parrots of the Wildmelds scientific exploration with features directed at the parrot enthusiast to inform and delight a broad audience.
eBook
Parrots of the wild : a natural history of the world's most captivating birds
\"A synthetic account of the diversity and ecology of wild parrots, distilling knowledge from the author's own research and from her review of more than 2,400 published scientific studies. The text covers parrots' evolutionary history, foraging, mating, and social behavior, innate intelligence, and conservation status. The book is enhanced by an array of illustrations, including photos of parrots taken exclusively in their natural habitat\"--Provided by publisher.
Book
The environmental consequences of climate-driven agricultural frontiers
Growing conditions for crops such as coffee and wine grapes are shifting to track climate change. Research on these crop responses has focused principally on impacts to food production impacts, but evidence is emerging that they may have serious environmental consequences as well. Recent research has documented potential environmental impacts of shifting cropping patterns, including impacts on water, wildlife, pollinator interaction, carbon storage and nature conservation, on national to global scales. Multiple crops will be moving in response to shifting climatic suitability, and the cumulative environmental effects of these multi-crop shifts at global scales is not known. Here we model for the first time multiple major global commodity crop suitability changes due to climate change, to estimate the impacts of new crop suitability on water, biodiversity and carbon storage. Areas that become newly suitable for one or more crops are Climate-driven Agricultural Frontiers. These frontiers cover an area equivalent to over 30% of the current agricultural land on the planet and have major potential impacts on biodiversity in tropical mountains, on water resources downstream and on carbon storage in high latitude lands. Frontier soils contain up to 177 Gt of C, which might be subject to release, which is the equivalent of over a century of current United States CO2 emissions. Watersheds serving over 1.8 billion people would be impacted by the cultivation of the climate-driven frontiers. Frontiers intersect 19 global biodiversity hotspots and the habitat of 20% of all global restricted range birds. Sound planning and management of climate-driven agricultural frontiers can therefore help reduce globally significant impacts on people, ecosystems and the climate system.
Journal Article
Individual identity information persists in learned calls of introduced parrot populations
Animals can actively encode different types of identity information in learned communication signals, such as group membership or individual identity. The social environments in which animals interact may favor different types of information, but whether identity information conveyed in learned signals is robust or responsive to social disruption over short evolutionary timescales is not well understood. We inferred the type of identity information that was most salient in vocal signals by combining computational tools, including supervised machine learning, with a conceptual framework of “hierarchical mapping”, or patterns of relative acoustic convergence across social scales. We used populations of a vocal learning species as a natural experiment to test whether the type of identity information emphasized in learned vocalizations changed in populations that experienced the social disruption of introduction into new parts of the world. We compared the social scales with the most salient identity information among native and introduced range monk parakeet ( Myiopsitta monachus ) calls recorded in Uruguay and the United States, respectively. We also evaluated whether the identity information emphasized in introduced range calls changed over time. To place our findings in an evolutionary context, we compared our results with another parrot species that exhibits well-established and distinctive regional vocal dialects that are consistent with signaling group identity. We found that both native and introduced range monk parakeet calls displayed the strongest convergence at the individual scale and minimal convergence within sites. We did not identify changes in the strength of acoustic convergence within sites over time in the introduced range calls. These results indicate that the individual identity information in learned vocalizations did not change over short evolutionary timescales in populations that experienced the social disruption of introduction. Our findings point to exciting new research directions about the robustness or responsiveness of communication systems over different evolutionary timescales.
Journal Article
Evidence for Vocal Learning and Limited Dispersal as Dual Mechanisms for Dialect Maintenance in a Parrot
Studies of avian vocal dialects commonly find evidence of geographic and acoustic stability in the face of substantial gene flow between dialects. The vocal imitation and reduced dispersal hypotheses are alternatives to explain this mismatch between vocal and genetic variation. We experimentally simulated dispersal in the yellow-naped amazon (Amazona auropalliata) by moving individuals within and across dialect boundaries in Costa Rica. One juvenile translocated across dialect boundaries altered its contact call to imitate the acoustic form of the local call six weeks post-release. In contrast, four adults translocated across dialect boundaries returned to their original capture site within 120 days, while five cross-dialect translocated adults who remained at the release site did not alter their contact calls. Translocated individuals were observed to show some segregation from resident flocks. The observation of vocal imitation by the juvenile bird supports the vocal imitation, whereas the behavior of adults is more consistent with the reduced dispersal hypotheses. Taken together, our results suggest that both post-dispersal learning by juveniles and high philopatry in adults could explain the stability of vocal dialects in the face of immigration and gene flow.
Journal Article
Migration speed, timing, and long‐term shifts in age structure in North American passerines during fall migration
Migration is challenging for birds, especially juveniles, who experience high mortality rates during migration. The challenge is exacerbated in the Anthropocene, contributing to widespread population declines. Conservation efforts focused on increasing juvenile survival could bolster population recovery. Understanding how age structure of the migrant community shifts throughout migration could inform conservation efforts and future questions of migration ecology. However, it is unknown whether the age structure of the migrant community shifts spatially or temporally during migration. To answer these questions, we first analyzed age‐related differences in migration speed and timing of departure during fall migration using 6 567 747 banding encounters, as variability in these components of migration could generate shifts in community demographics. We found widespread differences in migration speed (km d−1) with adults being faster than juveniles in most species, and departure timing differences tied to adult molt. Our analyses revealed shifts in community demographics, with the proportion of juveniles within the community decreasing at northerly latitudes throughout migration. We also determined that demographics have shifted over 53 years, with the proportion of juveniles increasing in the north, and decreasing in the south. Our findings contribute to our knowledge of migration ecology, and our understanding of community shifts over time.
Journal Article
An integrative measure of cognitive performance, but not individual task performance, is linked to male reproductive output in budgerigars
Cognitive abilities such as learning and memory are key for survival and reproduction. Individuals with high cognitive abilities may be more successful at attracting mates and producing offspring. However, empirical tests of and evidence supporting this hypothesis remain scarce. We measured cognitive performance of male budgerigars in four tasks: problem solving, detour reaching, seed discrimination, and spatial memory. We then tested female choice for male cognition at three stages of the mating choice process: social pairing, extra-pair mating, and continued reproductive investment with a social mate. We also measured female reproductive output. We used an integrative measure of male cognitive performance that encapsulates performance across all tasks, the ‘composite cognitive score’ by summing performance on the four tasks. In the first stage, females did not choose their social mates based on any of the measures of male cognitive performance. In the second stage, however, males with higher composite cognitive scores sired and raised more offspring. In the third stage, females increased their reproductive investment after the first breeding attempt when paired with males with higher detour-reaching scores. These results suggest that female reproductive decisions may shape overall male cognitive performance.
Journal Article