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Pest insects damage crops, transmit diseases, and are household nuisances. Historically, they have been controlled with insecticides, but overuse often leads to resistance to one or more of these chemicals. Insects gain resistance to insecticides through behavioral, metabolic, genetic, and physical mechanisms. One frequently overlooked strategy is through the use of ATP-binding cassette (ABC) transporters. ABC transporters, present in all domains of life, perform natural excretory functions, thus the exploitation of these transporters to excrete insecticides and contribute to resistance is highly plausible. Previous work has implicated ABC transporters in some cases of insecticide resistance. Proposed herein is a framework meant as a formal guide for more easily incorporating the analysis of ABC transporters into existing resistance monitoring using suggested simple research methods. This framework functions as a simple decision tree and its utility is demonstrated using case examples. Determining a role for ABC transporters in insecticide resistance would help to shape future resistance management plans and guide the design of new insecticides.

We review and synthesize information on invasions of nonnative forest insects and diseases in the United States, including their ecological and economic impacts, pathways of arrival, distribution within the United States, and policy options for reducing future invasions. Nonnative insects have accumulated in United States forests at a rate of

In many forested ecosystems, the architecture and functional ecology of certain tree species define forest structure and their species-specific traits control ecosystem dynamics. Such foundation tree species are declining throughout the world due to introductions and outbreaks of pests and pathogens, selective removal of individual taxa, and over-harvesting. Through a series of case studies, we show that the loss of foundation tree species changes the local environment on which a variety of other species depend; how this disrupts fundamental ecosystem processes, including rates of decomposition, nutrient fluxes, carbon sequestration, and energy flow; and dramatically alters the dynamics of associated aquatic ecosystems. Forests in which dynamics are controlled by one or a few foundation species appear to be dominated by a small number of strong interactions and may be highly susceptible to alternating between stable states following even small perturbations. The ongoing decline of many foundation species provides a set of important, albeit unfortunate, opportunities to develop the research tools, models, and metrics needed to identify foundation species, anticipate the cascade of immediate, short- and long-term changes in ecosystem structure and function that will follow from their loss, and provide options for remedial conservation and management.

Major efforts are underway to harness the carbon sequestration capacity of forests to combat global climate change. However, tree damage and death associated with insect and disease disturbance can reduce this carbon sequestration capacity. We quantified average annual changes in live tree carbon accumulation associated with insect and disease disturbances utilizing the most recent (2001 – 2019) remeasurement data from National Forest Inventory plots in the contiguous United States. Forest plots recently impacted by insect disturbance sequestered on average 69% less carbon in live trees than plots with no recent disturbance, and plots recently impacted by disease disturbance sequestered on average 28% less carbon in live trees than plots with no recent disturbance. Nationally, we estimate that carbon sequestration by live trees, defined as the estimated average annual rate of above- and belowground carbon accumulation in live trees (diameter at breast height ≥ 2.54 cm) on forest land, has been reduced by 9.33 teragrams carbon per year (95% confidence interval: 7.11 to 11.58) in forests that have experienced recent insect disturbance and 3.49 teragrams carbon per year (95% confidence interval: 1.30 to 5.70) in forests that have experienced recent disease disturbance, for a total reduction of 12.83 teragrams carbon per year (95% confidence interval: 8.41 to 17.28). Strengthened international trade policies and phytosanitary standards as well as improved forest management have the potential to protect forests and their natural capacity to contribute to climate change mitigation.

Chromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those from nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (≥3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched for important cell type–specific genes; and (iii) GWAS variants associated with traits relevant to a particular cell type are more enriched in stretch enhancers compared with short enhancers. Reporter constructs containing stretch enhancer sequences exhibited tissue-specific activity in cell culture experiments and in transgenic mice. These results suggest that stretch enhancers are critical chromatin elements for coordinating cell type–specific regulatory programs and that sequence variation in stretch enhancers affects risk of major common human diseases.

Abstract Background More than 28 000 people were infected with Ebola virus during the 2014–2015 West African outbreak, resulting in more than 11 000 deaths. Better methods are needed to reduce the risk of self-contamination while doffing personal protective equipment (PPE) to prevent pathogen transmission. Methods A set of interventions based on previously identified failure modes was designed to mitigate the risk of self- contamination during PPE doffing. These interventions were tested in a randomized controlled trial of 48 participants with no prior experience doffing enhanced PPE. Contamination was simulated using a fluorescent tracer slurry and fluorescent polystyrene latex spheres (PLSs). Self-contamination of scrubs and skin was measured using ultraviolet light visualization and swabbing followed by microscopy, respectively. Doffing sessions were videotaped and reviewed to score standardized teamwork behaviors. Results Participants in the intervention group contaminated significantly fewer body sites than those in the control group (median [interquartile range], 6 [3–8] vs 11 [6–13], P = .002). The median contamination score was lower for the intervention group than the control group when measured by ultraviolet light visualization (23.15 vs 64.45, P = .004) and PLS swabbing (72.4 vs 144.8, P = .001). The mean teamwork score was greater in the intervention group (42.2 vs 27.5, P < .001). Conclusions An intervention package addressing the PPE doffing task, tools, environment, and teamwork skills significantly reduced the amount of self-contamination by study participants. These elements can be incorporated into PPE guidance and training to reduce the risk of pathogen transmission. An intervention package that addressed components of the task, tools, environment, and teamwork skills during personal protective equipment (PPE) doffing significantly reduced the amount of self-contamination by study participants. These elements can be incorporated into PPE guidance and training to prevent pathogen transmission.

Fungal hyphal growth and branching are essential traits that allow fungi to spread and proliferate in many environments. This sustained growth is essential for a myriad of applications in health, agriculture, and industry. However, comparisons between different fungi are difficult in the absence of standardized metrics. Here, we used a microfluidic device featuring four different maze patterns to compare the growth velocity and branching frequency of fourteen filamentous fungi. These measurements result from the collective work of several labs in the form of a competition named the “Fungus Olympics.” The competing fungi included five ascomycete species (ten strains total), two basidiomycete species, and two zygomycete species. We found that growth velocity within a straight channel varied from 1 to 4 μm/min. We also found that the time to complete mazes when fungal hyphae branched or turned at various angles did not correlate with linear growth velocity. We discovered that fungi in our study used one of two distinct strategies to traverse mazes: high-frequency branching in which all possible paths were explored, and low-frequency branching in which only one or two paths were explored. While the high-frequency branching helped fungi escape mazes with sharp turns faster, the low-frequency turning had a significant advantage in mazes with shallower turns. Future work will more systematically examine these trends.

Transcription factor paralogs may share a common role in staged or overlapping expression in specific tissues, as in the Hox family. In other cases, family members have distinct roles in a range of embryologic, differentiation or response pathways (as in the Tbx and Pax families). For the interferon regulatory factor (IRF) family of transcription factors, mice deficient in Irf1 , Irf2 , Irf3 , Irf4 , Irf5 , Irf7 , Irf8 or Irf9 have defects in the immune response but show no embryologic abnormalities 1 , 2 , 3 , 4 , 5 , 6 , 7 . Mice deficient for Irf6 have not been reported, but in humans, mutations in IRF6 cause two mendelian orofacial clefting syndromes 8 , 9 , 10 , and genetic variation in IRF6 confers risk for isolated cleft lip and palate 11 , 12 , 13 , 14 , 15 . Here we report that mice deficient for Irf6 have abnormal skin, limb and craniofacial development. Histological and gene expression analyses indicate that the primary defect is in keratinocyte differentiation and proliferation. This study describes a new role for an IRF family member in epidermal development.

Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination. Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development. Pattern of HIV growth and antibody formation Hua-Xin Liao et al . followed the evolution of an HIV-1 virus, and the concurrent co-evolution of a CD4-binding-site broadly neutralizing antibody (BnAb), from the time of infection of a single African patient for a period of more than 3 years. The neutralizing antibody, of CH103 lineage, is a new type of BnAb that binds in a completely loop-based manner that differs from that of VRC01 class monoclonal antibodies — the CH103 lineage is less mutated, with fewer unusual macromutations and may be easier to induce. This work has implications for HIV vaccine development, suggesting viral strains that might generate broadly neutralizing antibodies within the host.

The subphylum Entomophthoromycotina (Phylum Zoopagomycota) includes many arthropod pathogens, some of which are renowned for their abilities to alter host behavior prior to death and cause epizootics that impact host populations. The last checklist of arthropod-pathogenic species in this group was published in 1963 and consisted of 39 species in a single genus. Since then, more species have been named, and their taxonomy has changed extensively. We have constructed an updated checklist for species of Entomophthoromycotina in North America; this checklist includes species in the continental United States, Canada, and Mexico. Data were compiled based on available published literature and metadata available from the ARSEF culture collection, adjusting names based on current taxonomy. In North America, the arthropod-pathogenic Entomophthoromycotina now include 80 species belonging to 14 genera, within two classes, plus one species in a form genus. This checklist provides a current framework for future studies of the biodiversity of this group of fungi.