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Global warming has been shifting climatic envelopes of many tree species to higher latitudes and elevations across the globe; however, unsuitable soil biota may inhibit tree migrations into these areas of suitable climate. Specifically, the role of mycorrhizal fungi in facilitating tree seedling establishment beyond natural species range limits has not been fully explored within forest ecosystems. We used three experiments to isolate and quantify the effects of mycorrhizal colonization and common mycorrhizal networks (CMN) on tree seedling survival and growth across (within and beyond) the elevational ranges of two dominant tree species in northeastern North America, which were associated with either arbuscular mycorrhiza (AMF, Acer saccharum) or ectomycorrhiza (EMF, Fagus grandifolia). In order to quantify the influence of mycorrhiza on seedling establishment independent of soil chemistry and climate, we grew seedlings in soils from within and beyond our study species ranges in a greenhouse experiment (GE) as well as in the field using a soil translocation experiment (STE) and another field experiment manipulating seedling connections to potential CMNs (CMNE). Root length colonized, seedling survival and growth, foliar nutrients, and the presence of potential root pathogens were examined as metrics influencing plant performance across species' ranges. Mycorrhizal inoculum from within species ranges, but not from outside, increased seedling survival and growth in a greenhouse setting; however, only seedling survival, and not growth, was significantly improved in field studies. Sustained potential connectivity to AMF networks increased seedling survival across the entire elevational range of A. saccharum. Although seedlings disconnected from a potential CMN did not suffer decreased foliar nutrient levels compared with connected seedlings, disconnected AM seedlings, but not EM seedlings, had significantly higher aluminum concentrations and more potential pathogens present. Our results indicate that mycorrhizal fungi may facilitate tree seedling establishment beyond species range boundaries in this forested ecosystem and that the magnitude of this effect is modulated by the dominant mycorrhizal type present (i.e., AM vs. EM). Thus, despite changing climate conditions beyond species ranges, a lack of suitable mutualists can still limit successful seedling establishment and stall adaptive climate‐induced shifts in tree species distributions. [ABSTRACT FROM AUTHOR]

Pear psylla, Cacopsylla pyricola (Foerster) (Hemiptera: Psyllidae), occurs as 2 seasonal morphotypes. Summerforms occur on pear (Pyrus communis L.; Rosales: Rosaceae) where they are a significant pest. The larger and darker winterform morphotype develops in response to shortening daylengths and begins winter in reproductive diapause characterized by the absence of ovarian development. Diapausing winterforms often leave pear to overwinter on coniferous shelter plants and then return to pear in late winter and early spring to begin depositing the eggs that produce the first summerform generation. Cacopsylla pyricola adults are attracted to the color of foliage most of the year, but little is known about the role of plant volatiles in host finding and in seasonal dispersal between host and shelter plants by the psyllid. We used a Y-tube olfactometer and choice assays to investigate the response by C. pyricola adults to volatiles emitted by pear and an evergreen tree (cypress) often used as a shelter plant by wintering C. pyricola. Attraction to pear and cypress volatiles varied by season, tree phenology, and psyllid physiology. Cacopsylla pyricola were attracted to cypress volatiles and preferred to settle on cypress shoots during winter and early spring but then shifted to a marked preference for the pear developmental host in late spring and summer. Female C. pyricola exhibited stronger responses to pear volatiles than did males. Our study is the first to show that plant volatiles have a role in host finding by C. pyricola and provides a foundation for research on chemical ecology and management of C. pyricola. [ABSTRACT FROM AUTHOR]

Approximately 14.7 million US children aged 2 to 19 years are obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution (Vd) for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased owing to increased lean body mass, blood volume, and decreased percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Association recommends that weight-based dosing should be used in patients ages <18 years who weigh <40 kg; weight-based dosing should be used in patients ≥40 kg, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in children diagnosed with overweight and obesity; and research efforts continue to evaluate dosing of medications in children diagnosed with overweight and obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: The pear psyllids comprise over 20 species of small, sap-feeding insects which include several of the most damaging pests in commercial pear orchards of Europe, temperate Asia, and the Americas. Efforts to control these pests historically have centered on the use of insecticides. Because psyllid outbreaks often may be prompted by insecticidal destruction of natural enemies, pear growers have begun to substitute biological control and conservation of natural enemies for some insecticide applications. Conservation of natural habitats to make alternative resources (prey and hosts) available to natural enemies of crop pests increasingly is being examined as a tactic for strengthening biological control in crops. This review shows that psyllids in natural habitats are important resources for species of predators and parasites which provide biocontrol of pear psyllids. Traits which affect suitability of non-pest psyllids to beneficials include how closely related they are to pear psyllids and type of seasonal life cycle, the latter shown to govern when (seasonally) non-pest psyllids in natural habitats are available to beneficials. Confirmation that natural habitats and these alternative resources lead to numerical increases in beneficials in orchards requires proof that key predators and parasites colonize orchards from natural habitats. Difficulties in obtaining this proof are discussed. The pear psyllids (Cacopsylla spp.; Psylloidea) comprise ~24 species of sap-feeding insects distributed in Europe, temperate Asia, and (as introductions) in the Americas. These pear-specialized insects are among the most damaging and difficult to control pests in orchards. Biological control increasingly is being used to replace or partially replace insecticidal management of pear psyllids. Many key natural enemies of pear psyllids regularly occur in non-orchard habitats on native plants. The presence of beneficial species both in orchard and non-orchard habitats (here referred to as "spillover") has prompted suggestions that native plants and their associated psyllids should be conserved as alternative resources for natural enemies of pear psyllids. The expectation is that the natural enemies will move from those habitats into psyllid-infested orchards. This review shows that psyllids in native habitats are important resources for several key predators and parasitoids of pear psyllids. These resources are critical enough that some beneficials exhibit an almost nomadic existence as they move between plant species, tracking the seasonal appearance and disappearance of psyllid species. In contrast, other natural enemies show minimal or no spillover between orchard and non-orchard habitats, which likely is evidence that they exhibit limited movement at best between orchard and non-orchard habitats. To show conclusively that spillover also indicates that a beneficial species disperses between native habitats and orchards requires difficult research on insect movement. This review concludes with a brief discussion of these difficulties and possible solutions. [ABSTRACT FROM AUTHOR]

Aims: The few remaining old-growth forests in the northeastern United States are often comprised of ectomycorrhizal (EM) tree-dominated patches surrounded by arbuscular mycorrhizal (AM) tree-dominated secondary forests. We examined how (1) distance from old growth and tree neighborhood composition influenced EM colonization, fungal richness, and fungal community composition of Betula lenta L. (black birch) seedlings, a common EM tree that colonizes abandoned agricultural fields, and (2) potential effects of EM fungal genera on seedling physiological performance. Methods: We sampled soils and tree composition from the edge of an EM-dominated old-growth forest into an adjacent AM-dominated secondary forest. We used soils to grow black birch seedlings in a growth chamber bioassay. We measured seedling EM colonization and investigated effects of EM fungi and soil characteristics on seedling physiological performance. Results: We identified 20 EM fungal species and found decreases in EM colonization and fungal richness with distance from old growth, with many taxa present only near the edge. Neighborhood EM tree abundance best explained EM colonization while distance interacted with EM tree basal area to best explain EM fungal richness of seedlings. Soils from neighborhoods lacking EM trees resulted in sparse EM colonization of seedlings. We found no clear effects of EM fungal genera on seedling performance, but we detected a slight decrease in seedling photosynthetic rate with distance from old growth. Conclusions: Old-growth forests can be reservoirs of EM fungi, and EM tree patches can function as localized inoculum sources in AM-dominated secondary forests, potentially facilitating EM tree establishment. [ABSTRACT FROM AUTHOR]

Cacopsylla pyricola (Förster) (Hemiptera: Psyllidae) is the most expensive and challenging insect pest of commercial pear trees in the Pacific Northwest. Integrated pest management (IPM) programs are working toward relying more heavily on natural enemies to reduce insecticide use. Trechnites insidiosus (Crawford) (Hymenoptera: Encyrtidae) is the main parasitoid of C. pyricola , but little is known about its biology in the region. Developing sampling tools is important for the deployment of IPM programs, including monitoring of natural enemies. In this study, we examined 2 conventional monitoring methods: beat trays and yellow sticky cards, in addition to screened sticky cards and 3D-printed cylinder traps. Additionally, we tested an overwintering trap for the collection of parasitized C. pyricola. The trapping methods were tested in orchards in Oregon and Washington. Unscreened cards caught the most T. insidiosus and C. pyricola , followed by screened cards, cylinder traps, and then beat trays. Beat trays sometimes failed to catch any T. insidiosus , even when it was found in abundance via other methods. Screened cards and cylinder traps reduced bycatch and increased ease of identifying T. insidiosus. Specimens from the cylinder traps were also more suitable for use in molecular analysis. The overwintering traps were effective at capturing parasitized C. pyricola , but were highly variable year to year. The ideal trapping method will vary based on research needs (e.g. DNA preservation, reducing bycatch, catching higher numbers), but both screened sticky cards and cylinder traps were viable methods for monitoring T. insidiosus and its host. [ABSTRACT FROM AUTHOR]

Tactics that manipulate insect behavior are a component of many pest management strategies. Pheromone-based mating disruption is one such tactic widely used in agricultural systems, but few studies have assessed disrupting other mate communication mechanisms, such as acoustic signals. The most destructive pear pest in the Pacific Northwest USA, pear psylla (Cacopsylla pyricola) is believed to use acoustic signals to find mates, making it a candidate for this type of disruption. This species has two adult morphs, overwintering adults (winterforms) that emerge in the spring and subsequent generations (summerforms). Our study characterized the mating signals for both sexes and morphs of pear psylla, and assessed whether temperature and previous exposure to adult conspecifics altered signals and likelihood of signaling. While there are descriptions for acoustic signals of other psyllid species, this study provides the first evidence that C. pyricola communicates acoustically. The two sexes communicate via duetting; males signal to attract a female and the female signals back if she is receptive for mating. We showed that both morphotypes' male signals contain a group of chirps followed by a trill, while females respond with chirps. Male signal trills differed significantly in frequency (Hz) between winterform and summerform psylla. The signal frequency among morphs also had a positive linear relationship with temperature, suggesting that dissimilarity in signals among morphs had some relationship to temperature. Males were more likely to signal when they had previous exposure to females compared to males without exposure to females. Our results provide new information on how pear psylla communicate acoustically for mating, advancing the potential to develop mating disruption strategies for integrated pest management (IPM). [ABSTRACT FROM AUTHOR]

The pear psyllids (Cacopsylla Ossiannilsson; Hemiptera: Psylloidea: Psyllidae) are a taxonomically difficult group of at least 24 species native to the Palaearctic region. One or more species occur in most pear-growing regions, in some cases as invasive introductions. Existing reviews of this group are primarily of taxonomic focus with limited overviews of biology. The earliest biological studies of the pear psyllids centered on a core group of a few western European species. In part, this focus arose because diversity of the pear psyllids was poorly understood. As taxonomic understanding has advanced over the last 3 decades, research has expanded taxonomically. Increasing difficulties in controlling the pear psyllids additionally has contributed to growth in research. Here, we review a now-extensive literature on diversity, biology, and management of the pear psyllids. Three broad observations emerged from this synthesis. First, large gaps in biological understanding of the pear psyllids persist for several geographic faunas, most notably for psyllids of the Eastern Palaearctic region. Second, taxonomic diversity is accompanied by biological diversity. Despite the commonality in host use among the pear psyllids, with each species being limited to development on Pyrus , striking differences exist among species in life cycles, wintering, and other biological traits. Third, many of the tools being used to manage pear psyllids today are in existence because of the long history of basic research which has targeted these pests. These tools include new insecticides of higher selectivity, various cultural and horticultural tactics, and practices that conserve natural enemies in orchards. [ABSTRACT FROM AUTHOR]

RT-PCR was used to test whether DNA from potato psyllid (Bactericera cockerelli (Šulc)) could be detected in generalist predators that had been allowed to feed on psyllids in laboratory feeding trials. The assay used primers that had been developed in Europe to amplify a region of the ITS2 gene in psyllids for use in identifying psyllid specimens intercepted at border inspection stations or discovered in regions currently free of the pest. We conducted feeding trials with arthropod generalist predators in diverse taxonomic groups (Araneae, Acari, and two orders of Insecta). RT-PCR readily detected potato psyllid DNA in predators that had recently fed upon the insect. DNA from a closely related psyllid, Bactericera dorsalis (Crawford), was not detected, suggesting that our approach is unlikely to lead to false positives. RT-PCR was found to be more sensitive than conventional PCR at detecting very dilute quantities of potato psyllid DNA. Predator taxa differed in how long after a feeding event prey DNA could be detected. Signal retention was longer in spiders and a predatory mite (Anystis) than in predatory true bugs (Hemiptera). We believe this new molecular tool will be of value in identifying potentially important sources of psyllid biological control under field conditions. [ABSTRACT FROM AUTHOR]

The desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromalderived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a critical role in driving cancer progression. Using fibroblast-derived matrices (FDMs), we show that cancer cells have increased growth on cancer associated FDMs, when compared to FDMs derived from non-malignant tissue (normal) fibroblasts. We assess the changes in ECM characteristics from normal to cancer-associated stroma at the primary tumor site. Compositional, structural, and mechanical analyses reveal significant differences, with an increase in abundance of core ECM proteins, coupled with an increase in stiffness and density in cancer-associated FDMs. From compositional changes of FDM, we derived a 36-ECM protein signature, which we show matches in large part with the changes in pancreatic ductal adenocarcinoma (PDAC) tumor and metastases progression. Additionally, this signature also matches at the transcriptomic level in multiple cancer types in patients, prognostic of their survival. Together, our results show relevance of FDMs for cancer modelling and identification of desmoplastic ECM components for further mechanistic studies. [ABSTRACT FROM AUTHOR]

With the current shortage of hospice/palliative care (HPC) workforce, there is an urgent need to train a generation of nurses with clinical competency in HPC to ensure equitable access and optimal care for patients living with serious illness or at the end of life. The recent demand for HPC teaching in nursing education calls for innovation in establishing clinical placements. Palliative care nursing experts in New York State were surveyed between June and August 2022 about facilitators of academic–clinical partnerships between nursing schools and clinical settings. Inductive content analysis of open-ended responses revealed six major interconnected themes: (a) Increase Awareness of HPC in the Nursing Program, (b) Build a Relationship With Administrators, (c) Look Beyond Acute Care Partnerships, (d) Offer Incentives, (e) Develop Direct Care Experiential Opportunities, and (f) Develop Non-Direct Care Experiential Opportunities. Findings provide rich insights into key considerations for successful collaboration between nursing schools and clinical sites. [Journal of Gerontological Nursing, 49(6), 13–18.] [ABSTRACT FROM AUTHOR]

The immunopathological mechanisms driving the development of severe COVID-19 remain poorly defined. Here, we utilize a rhesus macaque model of acute SARS-CoV-2 infection to delineate perturbations in the innate immune system. SARS-CoV-2 initiates a rapid infiltration of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and a significant increase of blood CD14-CD16+ monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generate a longitudinal scRNA-Seq dataset of airway cells, and map these subsets to corresponding populations in the human lung. SARS-CoV-2 infection elicits a rapid recruitment of two macrophage subsets: CD163+MRC1-, and TREM2+ populations that are the predominant source of inflammatory cytokines. Treatment with baricitinib (Olumiant®), a JAK1/2 inhibitor is effective in eliminating the influx of non-alveolar macrophages, with a reduction of inflammatory cytokines. This study delineates the major lung macrophage subsets driving airway inflammation during SARS-CoV-2 infection. 'The induction and coordination of immune cells in response to SARS-CoV-2 infection are critical in the immunopathology of COVID-19. Here the authors use a rhesus macaque model of SARS-CoV-2 infection and show key populations of macrophage drive the inflammatory cytokine production in the alveolar space'. [ABSTRACT FROM AUTHOR]

The eastern deciduous forest is a mix of arbuscular (AM) and ectomycorrhizal (EM) trees, but land use legacies have increased the abundance of AM trees like Acer spp. (maple). Although these legacies have not changed the abundance of some EM trees like Betula spp. (birch), EM conifers like Tsuga canadensis (hemlock), and Pinus strobus (pine) have declined. We used a soil bioassay to investigate if the microbial community near EM birch (birch soil) contains a greater abundance and diversity of EM fungal propagules compatible with T. canadensis and P. strobus compared to the community associated with the surrounding AM-dominated secondary forest matrix (maple soil). We also tested the effectiveness of inoculation with soil from a nearby EM-dominated old-growth forest as a restoration tool to reintroduce EM fungi into secondary forest soils. Finally, we examined how seedling growth responded to EM fungi associated with each treatment. Seedlings grown with birch soil were colonized by EM fungi mostly absent from the surrounding maple forest. Hemlock seedlings grown with birch soil grew larger than hemlock seedlings grown with maple soil, but pine seedling growth did not differ with soil treatment. The addition of old-growth soil inoculum increased hemlock and pine growth in both soils. Our results found that EM trees are associated with beneficial EM fungi that are mostly absent from the surrounding AM-dominated secondary forest, but inoculation with old-growth soil is effective in promoting the growth of seedlings by reintroducing native EM fungi to the AM-dominated forests. [ABSTRACT FROM AUTHOR]

Bactericera cockerelli (Šulc) (Hemiptera: Triozidae) is a vector of ' Candidatus Liberibacter solanacearum' (Lso), the pathogen that causes potato zebra chip. Zebra chip incidence varies regionally, perhaps because of geographic differences in species of noncrop hosts available to the vector and in susceptibility of those hosts to Lso. Native and introduced species of Lycium (Solanales: Solanaceae) are important noncrop hosts of B. cockerelli in some regions of North America. Susceptibility of native Lycium species to Lso is uncertain. We investigated the use of two native species of Lycium by B. cockerelli in South Texas and tested whether they are susceptible to Lso. Bactericera cockerelli adults and nymphs were collected frequently from L. berlandieri Dunal and L. carolinianum Walter. Greenhouse assays confirmed that B. cockerelli develops on both species and showed that Lso infects L. carolinianum. Molecular gut content analysis provided evidence that B. cockerelli adults disperse between potato and Lycium. These results demonstrate that L. berlandieri and L. carolinianum are likely noncrop sources of potato-colonizing B. cockerelli in South Texas and that L. carolinianum is a potential source of Lso-infected psyllids. We also routinely collected the congeneric psyllid, Bactericera dorsalis (Crawford), from both Lycium species. These records are the first for this psyllid in Texas. Bactericera dorsalis completed development on both native Lycium species, albeit with high rates of mortality on L. berlandieri. B. dorsalis acquired and transmitted Lso on L. carolinianum under greenhouse conditions but did not transmit Lso to potato. These results document a previously unknown vector of Lso. [ABSTRACT FROM AUTHOR]

Eleven haplotypes of the bacterium, 'Candidatus Liberibacter solanacearum', have been identified worldwide, several of which infect important agricultural crops. In the United States, haplotypes A and B are associated with yield and quality losses in potato, tomato, and other crops of the Solanaceae. Both haplotypes are vectored by potato psyllid, Bactericera cockerelli. Recently, a third haplotype, designated F, was identified in southern Oregon potato fields. To identify the vector of this haplotype, psyllids of multiple species were collected from yellow sticky cards placed near potato fields during two growing seasons. Over 2700 specimens were tested for 'Ca. L. solanacearum' by polymerase chain reaction. Forty-seven psyllids harbored the bacterium. The infected specimens comprised four psyllid species in two families, Aphalaridae and Triozidae (Hemiptera: Psylloidea). Nucleic acid and/or amino acid sequence analysis of the 'Ca. L. solanacearum' 16S ribosomal RNA, 50S ribosomal proteins L10/L12, and outer membrane protein identified three new haplotypes of the bacterium, designated as Aph1, Aph2 and Aph3, including two variants of Aph2 (Aph2a and Aph2b). The impact of these new haplotypes on solanaceous or other crops is not known. The vector of 'Ca. L. solanacearum' haplotype F was not detected in this study. [ABSTRACT FROM AUTHOR]

Epigenetically targeted therapeutic development, particularly for SAM-dependent methylations of DNA, mRNA and histones has been proceeding rapidly for cancer treatments over the past few years. However, this approach has barely begun to be exploited for developing new antibiotics, despite an overwhelming global need to counter antimicrobial resistance. Here, we explore whether SAM analogues, some of which are in (pre)clinical studies as inhibitors of human epigenetic enzymes, can also inhibit Clostridioides difficile-specific DNA adenine methyltransferase (CamA), a sporulation regulator present in all C. difficile genomes sequenced to date, but found in almost no other bacteria. We found that SGC0946 (an inhibitor of DOT1L), JNJ-64619178 (an inhibitor of PRMT5) and SGC8158 (an inhibitor of PRMT7) inhibit CamA enzymatic activity in vitro at low micromolar concentrations. Structural investigation of the ternary complexes of CamA-DNA in the presence of SGC0946 or SGC8158 revealed conformational rearrangements of the N-terminal arm, with no apparent disturbance of the active site. This N-terminal arm and its modulation of exchanges between SAM (the methyl donor) and SAH (the reaction product) during catalysis of methyl transfer are, to date, unique to CamA. Our work presents a substantial first step in generating potent and selective inhibitors of CamA that would serve in the near term as chemical probes to investigate the cellular mechanism(s) of CamA in controlling spore formation and colonization, and eventually as therapeutic antivirulence agents useful in treating C. difficile infection. [ABSTRACT FROM AUTHOR]

There has been particular interest in the deployment of digital pathology (DP) and artificial intelligence (AI) in the diagnosis of prostate cancer, but little is known about the views of the public on their use. Prostate Cancer UK supporters were invited to an online survey which included quantitative and qualitative questions exploring views on the use of DP and AI in histopathological assessment. A total of 1276 responses to the survey were analysed (response rate 12.5%). Most respondents were supportive of DP (87%, 1113/1276) and of testing AI in clinical practice as a diagnostic adjunct (83%, 1058/1276). Respondents saw DP as potentially increasing workflow efficiency, facilitating research, education/training and fostering clinical discussions between clinician and patient. Some respondents raised concerns regarding data security, reliability and the need for human oversight. Among those who were unsure about AI, information was requested regarding its performance and others wanted to defer the decision to use it to an expert. Although most are in favour of its use, some are unsure, and their concerns could be addressed with more information or better communication. A small minority (<1%) are not in favour of the testing of the use of AI in histopathology for reasons which are not easily addressed. [ABSTRACT FROM AUTHOR]

Insects harbor bacterial endosymbionts that provide their hosts with nutritional benefit or with protection against natural enemies, plant defenses, insecticides, or abiotic stresses. We used directed sequencing of 16S rDNA to identify and compare endosymbionts of Bactericera maculipennis (Crawford) and the western, central, and northwestern haplotypes of B. cockerelli (Šulc) (Hemiptera: Psylloidea: Triozidae). Both species are native to North America, are known to harbor the plant pathogen 'Candidatus Liberibacter solanacearum' and develop on shared host plants within the Convolvulaceae. The Old-World species Heterotrioza chenopodii (Reuter) (Psylloidea: Triozidae), now found in North America, was included as an outgroup. 16S sequencing confirmed that both Bactericera species harbor 'Candidatus Liberibacter solanacearum' and revealed that both species harbor unique strains of Wolbachia and Sodalis. However, the presence of Wolbachia and Sodalis varied among haplotypes of B. cockerelli. The central and western haplotypes harbored the same strains of Wolbachia, which was confirmed by Sanger sequencing of the wsp and ftsZ genes. Wolbachia was also detected in very low abundance from the northwestern haplotype by high-throughput sequencing of 16S but was not detected from this haplotype by PCR screening. The northwestern and central haplotypes also harbored Sodalis, which was not detected in the western haplotype. Heterotrioza chenopodii harbored an entirely different community of potential endosymbionts compared with the Bactericera spp. that included Rickettsia and an unidentified bacterium in the Enterobacteriaceae. Results of this study provide a foundation for further research on the interactions between psyllids and their bacterial endosymbionts. [ABSTRACT FROM AUTHOR]

Understanding host use by psyllids (Hemiptera: Psylloidea) benefits from comparative studies of behavior on host and nonhost plant species. While most psyllid species develop on one or a few closely related plant species, some species are generalized enough to develop on species across plant families. We used electropenetography (EPG) technology to compare probing activities of an oligophagous psyllid (Bactericera cockerelli (Šulc)) and a host-specialized psyllid (Bactericera maculipennis) on two species of Solanaceae (potato, Solanum tuberosum L. and matrimony vine, Lycium barbarum L.) and two species of Convolvulaceae (field bindweed, Convolvulus arvensis L. and sweet potato, Ipomoea batatas). Bactericera cockerelli develops on all four species, albeit with longer development times on Convolvulaceae. Bactericera maculipennis develops only on Convolvulaceae. Bactericera cockerelli fed readily from phloem of all four species, but the likelihood of entering phloem and duration of time in phloem was reduced on suboptimal hosts (Convolvulaceae) relative to behavior on Solanaceae. We observed instances of cycling between bouts of phloem salivation and ingestion in assays of optimal (Solanaceae) hosts not observed on Convolvulaceae. The Convolvulaceae-specialized B. maculipennis (Crawford) failed to feed from phloem of nonhosts (Solanaceae). Both psyllid species readily ingested from xylem of all plant species, irrespective of host status. Our finding that phloem feeding by B. maculipennis did not occur on potato has implications for understanding epidemiology of phloem-limited psyllid-vectored plant pathogens. Our results also showed that EPG assays detect subtle variation in probing activities that assist in understanding host use by psyllids. [ABSTRACT FROM AUTHOR]

The quantification of airway compliance (Caw) is essential to the study of airway alterations in disease models. However, the required measurements of airway pressure and volume are difficult to acquire in mice. We hypothesized that the inflation limb of full-range pressure-volume (PV) curves could be used to quantify Caw, as it contains a segment where only the airway tree is distended. The study objective was to assess the feasibility of the approach by analysis of full-range PV curves previously collected in three mouse models: an elastase model of emphysema, a genetic model spontaneously developing emphysema (leukotriene C4 synthase knockout; LTC4S-KO), and a bleomycin model of lung fibrosis. Attempts to validate results included Caw change relative to respiratory system compliance (ΔCaw/ΔC), the minute work of breathing (mWOB), and the elastance at 20.5 Hz (Ers_20.5) from prior respiratory mechanics measurements in the same subjects. Caw was estimated at 3% of total compliance in healthy mice or 2.3 ± 1 μL/cmH2O (n = 17). The technique detected changes in models of respiratory obstructive and restrictive diseases relative to control mice as well as differences in the two emphysema models studied. The changes in Caw were consistent with those seen in ΔCaw/ΔC, mWOB, or Ers_20.5, with some variations according to the model, as well as with results reported in the literature in humans and mice. Direct Caw measurements in subjects as small as mice could prove useful to further characterize other respiratory disease models associated with airway remodeling or to assess treatment effects. [ABSTRACT FROM AUTHOR]

The Psylloidea (Hemiptera) comprise ~4,000 species of small sap-feeding insects known as psyllids or jumping plant-lice. We summarize species composition of the nonnative psyllid fauna in North America and review detection records, current distributions, host use, life histories, and geographical sources. Forty-six species are considered to be nonnative accounting for ~10% of the known North American psyllid fauna. The family Psyllidae is overrepresented in the pool of exotics (52% of exotic species) relative to global psyllid diversity, whereas Triozidae (at 11% of exotic species) is underrepresented. Records of initial detection range from the 1832 detection of a European pear psyllid to the 2016 detection of a Ficus specialist from Asia. Many species exhibit discontinuous distributions in North America presumably caused by multiple introductions or by secondary spread of established populations. Host plants of nonnative species are almost exclusively trees and shrubs. The factor most correlated with introduction is presence of hosts from the psyllid's native region. Virtually all host plants in North America have been imported intentionally for human-related use, with initial importation beginning in the 1500s and 1600s. Arrival of host plants in North America often preceded psyllid detection or arrival by decades or centuries. There has been almost no spillover by psyllids onto native plant species reflecting the narrow host range of Psylloidea. A glaring exception is the recent damaging colonization of a native Fraxinus closely related to the psyllid's European Fraxinus host. Biological and geographical traits correlated with arrival and establishment of nonnative psyllids have shifted through time. Temperate Europe was the source of the earliest arriving species, with initial detection records primarily in New England and eastern Canada. In contrast, recent arrivals are mostly Myrtaceae- and Fabaceae-feeding species from the Neotropics or Australia, with detection records limited mostly to Florida or California. Early-arriving, temperate zone species exhibit a formal winter diapause while recent arrivals from the Neotropics and Australia appear to reproduce more-or-less continuously. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infections are an urgent medical problem. The newly discovered C.difficileadenine methyltransferase A (CamA) is specified by all C. difficile genomes sequenced to date (>300), but is rare among other bacteria. CamA is an orphan methyltransferase, unassociated with a restriction endonuclease. CamA-mediated methylation at CAAAAA is required for normal sporulation, biofilm formation, and intestinal colonization by C. difficile. We characterized CamA kinetic parameters, and determined its structure bound to DNA containing the recognition sequence. CamA contains an N-terminal domain for catalyzing methyl transfer, and a C-terminal DNA recognition domain. Major and minor groove DNA contacts in the recognition site involve base-specific hydrogen bonds, van der Waals contacts and the Watson-Crick pairing of a rearranged A:T base pair. These provide sufficient sequence discrimination to ensure high specificity. Finally, the surprisingly weak binding of the methyl donor S-adenosyl-l-methionine (SAM) might provide avenues for inhibiting CamA activity using SAM analogs. Clostridioides difficile adenine methyltransferase A (CamA) is required for the sporulation and colonization of the pathogen that causes gastrointestinal infections. Here, the authors characterise CamA kinetically and present its crystal structure bound to the DNA recognition sequence, which reveals DNA distortions including bending and the flipping of the target adenine out of the DNA helix, as well as protein conformational changes upon cofactor binding. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment (TME), and are associated with a poor clinical prognosis. However, despite recent advances in understanding neutrophil biology in cancer, therapies targeting tumor-associated neutrophils are lacking. Here, we demonstrate, using pre-clinical mouse models of PDAC, that lorlatinib attenuates PDAC progression by suppressing neutrophil development and mobilization, and by modulating tumor-promoting neutrophil functions within the TME. When combined, lorlatinib also improves the response to anti-PD-1 blockade resulting in more activated CD8 + T cells in PDAC tumors. In summary, this study identifies an effect of lorlatinib in modulating tumor-associated neutrophils, and demonstrates the potential of lorlatinib to treat PDAC. Tumor associated neutrophils have been correlated with poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). Here the authors show that the tyrosine kinase inhibitor lorlatinib modulates neutrophil development and recruitment in the tumor microenvironment, attenuating PDAC progression in preclinical mouse models. [ABSTRACT FROM AUTHOR]

Changing climate and land‐use practices have the potential to bring previously isolated populations of pest insects into new sympatry. This heightens the need to better understand how differing patterns of host–plant association, and unique endosymbionts, serve to promote genetic isolation or integration. We addressed these factors in populations of potato psyllid, Bactericera cockerelli (Šulc), a generalist herbivore that vectors a bacterial pathogen (Candidatus Liberibacter solanacearum, causal pathogen of zebra chip disease) of potato (Solanum tuberosum L.). Genome‐wide SNP data revealed two major genetic clusters—psyllids collected from potato crops were genetically similar to psyllids found on a common weed, Lycium spp., but dissimilar from those found on another common non‐crop host, Solanum dulcamara L. Most psyllids found on Lycium spp. and potato represented a single mitochondrial cytochrome oxidase I (COI) haplotype that has been suggested to not be native to the region, and whose arrival may have been concurrent with zebra chip disease first emerging. The putatively introduced COI haplotype usually co‐occurred with endosymbiotic Wolbachia, while the putatively resident COI haplotype generally did not. Genetic intermediates between the two genetic populations of insects were rare, consistent with recent sympatry or reproductive isolation, although admixture patterns of apparent hybrids were consistent with introgression of genes from introduced into resident populations. Our results suggest that both host–plant associations and endosymbionts are shaping the population genetic structure of sympatric psyllid populations associated with different non‐crop hosts. It is of future interest to explicitly examine vectorial capacity of the two populations and their potential hybrids, as population structure and hybridization might alter regional vector capacity and disease outbreaks. [ABSTRACT FROM AUTHOR]

The potato psyllid, Bactericera cockerelli (Šulc), is a major pest of potato (Solanum tuberosum L.; Solanales: Solanaceae) as a vector of ' Candidatus Liberibacter solanacearum', the pathogen that causes zebra chip. Management of zebra chip is challenging in part because the noncrop sources of Liberibacter-infected psyllids arriving in potato remain unknown. Adding to this challenge is the occurrence of distinct genetic haplotypes of both potato psyllid and Liberibacter that differ in host range. Longleaf groundcherry (Physalis longifolia Nutt.) has been substantially overlooked in prior research as a potential noncrop source of Liberibacter-infected B. cockerelli colonizing fields of potato. The objective of this study was to assess the suitability of P. longifolia to the three common haplotypes of B. cockerelli (central, western, and northwestern haplotypes), and to two haplotypes of ' Ca. L. solanacearum' (Liberibacter A and B haplotypes). Greenhouse bioassays indicated that B. cockerelli of all three haplotypes produced more offspring on P. longifolia than on potato and preferred P. longifolia over potato during settling and egg-laying activities. Greenhouse and field trials showed that P. longifolia was also highly susceptible to Liberibacter. Additionally, we discovered that infected rhizomes survived winter and produced infected plants in late spring that could then be available for psyllid colonization and pathogen acquisition. Results show that P. longifolia is susceptible to both B. cockerelli and ' Ca. L. solanacearum' and must be considered as a potentially important source of infective B. cockerelli colonizing potato fields in the western United States. [ABSTRACT FROM AUTHOR]

Our previous study provided correlative evidence that morning glory species harboring endophytic fungi (Periglandula) are resistant to potato psyllid [ Bactericera cockerelli (Šulc)], whereas species free of fungi often allowed psyllid development. In this study, we manipulated levels of ergot alkaloids in host tissues by inoculating clippings from potato plants with extracts from morning glories that harbor Periglandula [ Ipomoea leptophylla Torrey, Ipomoea imperati (Vahl) Grisebach, Ipomoea tricolor Cavanilles, Ipomoea pandurata (L.) G. F. Meyer, and Turbina corymbosa (L.)] and one species (Ipomoea alba L.) that does not harbor the endophyte. Ergot alkaloids (clavines, lysergic acid amides, and ergopeptines) were detected in potato clippings, thus confirming that leaves had taken up compounds from solutions of crude extracts. Psyllid mortality rates on inoculated clippings ranged between 53 and 93% in treatments producing biochemically detectable levels of alkaloids, when compared with 15% mortality in water controls or the alkaloid-free I. alba. We then tested synthetic analogs from each of the three alkaloid classes that had been detected in the crude extracts. Each compound was assayed by inoculating clippings of two host species (potato and tomato) at increasing concentrations (0, 1, 10, and 100 µg/ml in solution). Psyllids exhibited a large and significant increase in mortality rate beginning at the lowest two concentrations, indicating that even very small quantities of these chemicals led to mortality. Feeding by nymphs on artificial diets containing synthetic compounds resulted in 100% mortality within 48 h, irrespective of compound. Further testing of ergot alkaloids to characterize the mode of action that leads to psyllid mortality is warranted. [ABSTRACT FROM AUTHOR]

Erythritol is a dietary sweetener that is used for low-calorie or diabetic diets. Although safe for human consumption, erythritol is lethal to certain Dipteran pests, but insecticidal effects of erythritol on phloem-feeding insects have yet to be examined. Our goal was to determine whether erythritol has insecticidal activity against pear psylla, Cacopsylla pyricola (Foerster) (Hemiptera: Psyllidae). We first demonstrated that ingestion of erythritol solutions compared with water by pear psylla caused reduced feeding, impaired motor functions, and reduced survival time of adults. We then tested whether foliar treatment of pear leaves with erythritol was also lethal to pear psylla. Foliar treatment of erythritol led to reduced 3-d survival of pear psylla nymphs and adults, and reduced rates of oviposition by pear psylla adults. Psylla adults also preferred to settle on untreated leaves than on erythritol-treated leaves in preference assays. Finally, we conducted field experiments to test whether applications of erythritol provided pear trees with protection against pear psylla under natural field conditions. Those experiments showed a reduction in pear psylla nymphs on erythritol-treated trees compared with untreated trees, but only if the erythritol was completely dissolved into solution by heating. Laboratory trials confirmed the importance of heating. Results of our experiments demonstrate that erythritol is insecticidal to pear psylla nymphs and adults and provide the first report that erythritol is lethal to a phloem-feeding insect. These findings suggest that erythritol may provide a new safe and effective tool for the management of pear psylla. [ABSTRACT FROM AUTHOR]

Objective: To review the efficacy and safety of niraparib for the treatment of recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (OC, FTC, and PPC).Data Sources: A literature search via MEDLINE through PubMed from August 2013 to January 2020 was performed using the key terms niraparib, PARP inhibitors, ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.Study Selection and Data Extraction: Completed and ongoing trials were identified through a review of the website trial registry https://www.clinicaltrials.gov.Data Synthesis: In a phase III, double-blind clinical trial, progression-free survival improved in patients treated with niraparib compared with placebo as maintenance treatment for patients with platinum-sensitive, recurrent OC: 21 versus 5.5 months in the germline breast cancer susceptibility gene (gBRCA) cohort (hazard ratio [HR] = 0.27; 95% CI = 0.17 to 0.41; P < 0.001) and 9.3 versus 3.9 months in the overall nongermline breast cancer susceptibility gene (non-gBRCA) cohort (HR = 0.45; 95% CI = 0.34 to 0.61; P < 0.001). Adverse events included thrombocytopenia and anemia.Relevance To Patient Care and Clinical Practice: Poly (ADP-ribose) polymerase (PARP) inhibitors have gained a place in the therapeutic management of OC, FTC, and PPC because of their ability to suppress growth of homologous recombination deficiency-positive tumors, including those with BRCA1/2 mutations. Niraparib inhibits the DNA repair mechanism vital to the survival of cancer cells, poly-ADP ribose polymerase.Conclusions: PARP inhibitors can be used as a single agent for maintenance therapy for platinum-sensitive recurrent disease in patients with partial or complete response following 2 or more rounds of platinum-based therapy. [ABSTRACT FROM AUTHOR]

Aims: Biological invasions have historically been addressed mostly from an aboveground perspective, so little is known about the impacts of belowground invasions. We studied the impact of belowground invasions on growth of native tree species and test the possibility of novel interactions between native and non-native hosts and native and non-native belowground symbionts. Methods: We combined field and growth chamber studies. With a growth chamber bioassay we compared growth and root colonization percentage of native Nothofagus and non-native invasive pine species, both highly dependent on ectomycorrhizal fungi (EMF), growing in pine invaded and non-invaded soils from native Nothofagus forest. We evaluated the identity of EMF species associated with both hosts in the different soil sources from the bioassay and we performed an in situ root sampling in the field. Results: We found that both hosts grew equally well in both soil sources in terms of biomass, with high percent of root colonization, and no cross-host colonization of symbiotic EMF except for one species of Sistotrema found on both hosts. Conclusions: Soil where invasive hosts are absent is already conditioned by the presence of non-native invasive EMF. Native trees may be able to remain in the invaded area due to the presence of native EMF. The presence of native hosts is not hindering the invasion of non-native hosts and the presence of native belowground fungal mutualists seems not to hinder the spread of their non-native counterparts. [ABSTRACT FROM AUTHOR]

Background: Studies suggest that acute decreases in lung hyperinflation at rest improves cardiac function and increases lung vascular perfusion from decompression of a compromised heart. In those studies, changes in resting oxygen uptake induced by medications, an alternative explanation for compensatory increased cardiac function, were not explored.Methods: This double-blind, multicenter, double-crossover study enrolled adults with chronic obstructive pulmonary disease, resting hyperinflation, and > 10% improvement in inspiratory capacity after 2 inhalations of budesonide/formoterol 160/4.5 μg. Metabolic, cardiac, and ventilatory function were measured 60 min pre-/post-dose at each visit. Primary endpoint was change in resting oxygen uptake for budesonide/formoterol versus placebo.Results: Fifty-one patients (median age: 63 years) received treatment. Compared with placebo, budesonide/formoterol significantly increased resting oxygen uptake (mean change from baseline: 1.25 vs 11.37 mL/min; P = 0.007) as well as tidal volume and minute ventilation. This occurred despite improvements in the inspiratory capacity, forced vital capacity, and expiratory volume in 1 s. No significant treatment differences were seen for oxygen saturation, respiratory rate, and resting dyspnea. There was a numerical increase in oxygen pulse (oxygen uptake/heart rate). Correlations between inspiratory capacity and oxygen pulse were weak.Conclusions: Budesonide/formoterol treatment in resting hyperinflated patients with COPD results in significant deflation. The increase in oxygen uptake and minute ventilation at lower lung volumes, without changes in heart rate and with minimal improvement in oxygen pulse, suggests increased oxygen demand as a contributor to increased cardiac function.Trial Registration: ClinicalTrials.gov identifier: NCT02533505. [ABSTRACT FROM AUTHOR]

Nonoptimal synonymous codons repress gene expression, but the underlying mechanisms are poorly understood. We and others have previously shown that nonoptimal codons slow translation elongation speeds and thereby trigger messenger RNA (mRNA) degradation. Nevertheless, transcript levels are often insufficient to explain protein levels, suggesting additional mechanisms by which codon usage regulates gene expression. Using reporters in human and Drosophila cells, we find that transcript levels account for less than half of the variation in protein abundance due to codon usage. This discrepancy is explained by translational differences whereby nonoptimal codons repress translation initiation. Nonoptimal transcripts are also less bound by the translation initiation factors eIF4E and eIF4G1, providing a mechanistic explanation for their reduced initiation rates. Importantly, translational repression can occur without mRNA decay and deadenylation, and it does not depend on the known nonoptimality sensor, CNOT3. Our results reveal a potent mechanism of regulation by codon usage where nonoptimal codons repress further rounds of translation. [Display omitted] • Synonymous codon usage impacts protein expression beyond mRNA levels • Nonoptimal transcripts are engaged by fewer ribosomes • Reduced eIF4E binding is required to repress translation initiation • Translational repression is not a consequence of mRNA decay nor deadenylation Barrington et al. demonstrate that nonoptimal codon usage reduces protein expression post-transcriptionally by repressing translation initiation. These findings reconcile a long-standing contradiction in the field between slow elongation speed and reduced ribosome occupancy and suggest that elongation and initiation machinery cooperate to regulate gene expression. [ABSTRACT FROM AUTHOR]

SETD3 is an actin histidine-N3 methyltransferase, whereas other characterized SET-domain enzymes are protein lysine methyltransferases. We report that in a pre-reactive complex SETD3 binds the N3-protonated form (N3-H) of actin His73, and in a post-reactive product complex, SETD3 generates the methylated histidine in an N1-protonated (N1-H) and N3-methylated form. During the reaction, the imidazole ring of His73 rotates ~105°, which shifts the proton from N3 to N1, thus ensuring that the target atom N3 is deprotonated prior to the methyl transfer. Under the conditions optimized for lysine deprotonation, SETD3 has weak lysine methylation activity on an actin peptide in which the target His73 is substituted by a lysine. The structure of SETD3 with Lys73-containing peptide reveals a bent conformation of Lys73, with its side chain aliphatic carbons tracing along the edge of imidazole ring and the terminal ε-amino group occupying a position nearly identical to the N3 atom of unmethylated histidine. [ABSTRACT FROM AUTHOR]

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Psyllids are phloem-feeding insects that tend to be highly specific in their host plants. Some species are well-known agricultural pests, often as vectors of plant pathogens. Many pest psyllids colonize agricultural fields from non-crop reproductive hosts or from non-host transitory and winter shelter plants. Uncertainty about which non-crop species serve as sources of psyllids hinders efforts to predict which fields or orchards are at greater risk of being colonized by psyllids.