A stable antimicrobial peptide with dual functions of treating and preventing citrus Huanglongbing.

Citrus Huanglongbing (HLB), caused by a vector-transmitted phloem-limited bacterium Candidatus Liberibacter asiaticus (CLas), is the most devastating citrus disease worldwide. Currently, there are no effective strategies to prevent infection or to cure HLB-positive trees. Here, using comparative analysis between HLB-sensitive citrus cultivars and HLB-tolerant citrus hybrids and relatives, we identified a novel class of stable antimicrobial peptides (SAMPs). The SAMP from Microcitrusaustraliasica can rapidly kill Liberibacter crescens (Lcr), a culturable Liberibacter strain, and inhibit infections of CLas and CL. solanacearum in plants. In controlled greenhouse trials, SAMP not only effectively reduced CLas titer and disease symptoms in HLB-positive trees but also induced innate immunity to prevent and inhibit infections. Importantly, unlike antibiotics, SAMP is heat stable, making it better suited for field applications. Spray-applied SAMP was taken up by citrus leaves, stayed stable inside the plants for at least a week, and moved systemically through the vascular system where CLas is located. We further demonstrate that SAMP is most effective on α-proteobacteria and causes rapid cytosol leakage and cell lysis. The α-helix-2 domain of SAMP is sufficient to kill Lcr Future field trials will help determine the efficacy of SAMP in controlling HLB and the ideal mode of application.

Transfer and biological effects of cadmium along a tomato - thrip - predatory bug food chain.

The heavy metal, cadmium (Cd) is an increasingly serious issue in agricultural ecosystems, mediating bottom-up effects on plants, herbivores and natural enemies. We measured how Cd modifies interactions between tomato Solanum lycopersicum, western flower thrips Frankliniella occidentalis, and the predatory bug Orius sauteri by examining Cd effects on the growth of tomato, the fitness of western flower thrips, and the survival and behavior of predators. The photosynthetic parameters of Pn (net photosynthetic rate), Gs (stomatal conductance), Ci (intercellular CO2 concentration), and Tr (transpiration rate) of tomato plants significantly decreased with the increase of Cd concentration. The total survival number of western flower thrips fed on tomato plants treated with different concentrations of Cd was significantly lower than that of the control, and sex ratios (female/male) gradually increased with the increase of Cd concentration. The numbers of thrips predated by O. sauteri on tomato plants treated with high concentrations of Cd (2.0 or 4.0 mg/L) were significantly reduced by the second day. Cadmium was accumulated and bioconcentrated in the roots, stems, leaves of tomato plants, and transferred to F. occidentalis, and O. sauteri. Cadmium translocated in significant quantities from roots to the stems and leaves of tomato plants, and from the tomato leaf to F. occidentalis. However, there was minimal (non-significant) transfer of Cd from F. occidentalis to O. sauteri. The presence of Cd significantly reduced the growth of tomato plants, the fitness of F. occidentalis, and the predation efficiency of O. sauteri. Collectively, Cd can mediate bottom-up effects on tomato, thrip, and predatory bug along food chain, potentially interrupting pest biological control in tomato in heavy metal-contaminated ecosystems.

Heavy metal exposure reduces larval gut microbiota diversity of the rice striped stem borer, Chilo suppressalis.

Cadmium (Cd), a widely distributed environmental pollutant in agroecosystems, causes negative effects on crops and herbivores through bottom-up processes. The gut microbial community of an insect can play a critical role in response to metal stress. To understand how microbiota affect the stress responses of organisms to heavy metals in agroecosystems, we initially used 16S rRNA sequencing to characterize the larval gut microbiota of Chilo suppressalis, an important agricultural pest, exposed to a diet containing Cd. The species richness, diversity, and composition of the gut microbial community was then analyzed. Results revealed that while the richness (Chao1 and ACE) of gut microbiota in larvae exposed to Cd was not significantly affected, diversity (Shannon and Simpson) was reduced due to changes in species distribution and relative abundance. Overall, the most abundant genus was Enterococcus, while the abundance of the genera Micrococcaceae and Faecalibaculum in the control significantly superior to that in Cd-exposed pests. Phylogenetic investigation of microbial communities by the reconstruction of unobserved states (PICRUSt) showed that the intestinal microorganisms appear to participate in 34 pathways, especially those used in environmental information processing and the metabolism of the organism. This study suggests that the gut microbiota of C. suppressalis are significantly impacted by Cd exposure and highlights the importance of the gut microbiome in host stress responses and negative effects of Cd pollution in agroecosystems.

Identification of citrus immune regulators involved in defence against Huanglongbing using a new functional screening system.

Huanglongbing (HLB) is the most devastating citrus disease in the world. Almost all commercial citrus varieties are susceptible to the causal bacterium, Candidatus Liberibacter asiaticus (CLas), which is transmitted by the Asian citrus psyllid (ACP). Currently, there are no effective management strategies to control HLB. HLB-tolerant traits have been reported in some citrus relatives and citrus hybrids, which offer a direct pathway for discovering natural defence regulators to combat HLB. Through comparative analysis of small RNA profiles and target gene expression between an HLB-tolerant citrus hybrid (Poncirus trifoliata × Citrus reticulata) and a susceptible citrus variety, we identified a panel of candidate defence regulators for HLB-tolerance. These regulators display similar expression patterns in another HLB-tolerant citrus relative, with a distinct genetic and geographic background, the Sydney hybrid (Microcitrus virgata). Because the functional validation of candidate regulators in tree crops is always challenging, we developed a novel rapid functional screening method, using a C. Liberibacter solanacearum (CLso)/potato psyllid/Nicotiana benthamiana interaction system to mimic the natural transmission and infection circuit of the HLB complex. When combined with efficient virus-induced gene silencing in N. benthamiana, this innovative and cost-effective screening method allows for rapid identification and functional characterization of regulators involved in plant immune responses against HLB, such as the positive regulator BRCA1-Associated Protein, and the negative regulator Vascular Associated Death Protein.

Contaminants of emerging concern affect Trichoplusia ni growth and development on artificial diets and a key host plant.

Many countries are utilizing reclaimed wastewater for agriculture because drought, rising temperatures, and expanding human populations are increasing water demands. Unfortunately, wastewater often contains biologically active, pseudopersistent pharmaceuticals, even after treatment. Runoff from farms and output from wastewater treatment plants also contribute high concentrations of pharmaceuticals to the environment. This study assessed the effects of common pharmaceuticals on an agricultural pest, Trichoplusia ni (Lepidoptera: Noctuidae). Larvae were reared on artificial diets spiked with contaminants of emerging concern (CECs) at environmentally relevant concentrations. Trichoplusia ni showed increased developmental time and mortality when reared on artificial diets containing antibiotics, hormones, or a mixture of contaminants. Mortality was also increased when T. ni were reared on tomatoes grown hydroponically with the same concentrations of antibiotics. The antibiotic-treated plants translocated ciprofloxacin through their tissues to roots, shoots, and leaves. Microbial communities of T. ni changed substantially between developmental stages and when exposed to CECs in their diets. Our results suggest that use of reclaimed wastewater for irrigation of crops can affect the developmental biology and microbial communities of an insect of agricultural importance.

Effects of contaminants of emerging concern on Myzus persicae (Sulzer, Hemiptera: Aphididae) biology and on their host plant, Capsicum annuum.

Many countries are utilizing reclaimed wastewater for agriculture as water demands due to drought, rising temperatures, and expanding human populations. Unfortunately, wastewater often contains biologically active, pseudopersistant pharmaceuticals, even after treatment. Runoff from agriculture and effluent from wastewater treatment plants also contribute high concentrations of pharmaceuticals to the environment. This study assessed the effects of common pharmaceuticals on an agricultural pest, the aphid Myzus persicae (Sulzer, Hemiptera: Aphididae). Second instar nymphs were transferred to bell peppers (Capsicum annuum) that were grown hydroponically. Treatment plants were spiked with contaminants of emerging concern (CECs) at environmentally relevant concentrations found in reclaimed wastewater. M. persicae displayed no differences in population growth or microbial community differences due to chemical treatments. Plants, however, displayed significant growth reduction in antibiotic and mixture treatments, specifically in wet root masses. Antibiotic treatment masses were significantly reduced in the total and root wet masses. Mixture treatments displayed an overall reduction in plant root wet mass. Our results suggest that the use of reclaimed wastewater for crop irrigation would not affect aphid populations, but could hinder or delay crop production.

Acute exposure to selenium disrupts associative conditioning and long-term memory recall in honey bees (Apis mellifera).

A plethora of toxic compounds - including pesticides, heavy metals, and metalloids - have been detected in honey bees (Apis mellifera) and their colonies. One such compound is selenium, which bees are exposed to by consuming nectar and pollen from flowers grown in contaminated areas. Though selenium is lethal at high concentrations, sublethal exposure may also impair honey bees' ability to function normally. Examining the effect of selenium exposure on learning and memory provides a sensitive assay with which to identify sublethal effects on honey bee health and behavior. To determine whether sublethal selenium exposure causes learning and memory deficits, we used proboscis extension reflex conditioning coupled with recall tests 30min and 24h post-conditioning. We exposed forager honey bees to a single sublethal dose of selenium, and 3h later we used an olfactory conditioning assay to train the bees to discriminate between one odor associated with sucrose-reinforcement and a second unreinforced odor. Following conditioning we tested short- and long-term recall of the task. Acute exposure to as little as 1.8ng of an inorganic form of selenium (sodium selenate) before conditioning caused a reduction in behavioral performance during conditioning. And, exposure to 18ng of either an inorganic form (sodium selenate) or an organic form (methylseleno-l-cysteine) of selenium caused a reduction in the bees' performance during the long-term recall test. These concentrations of selenium are lower than those found in the nectar of plants grown in selenium-contaminated soil, indicating that even low-grade selenium toxicity produces significant learning and memory impairments. This may reduce foragers' ability to effectively gather resources for the colony or nurse bees' ability to care for and maintain a healthy colony.

Cadmium, copper, and lead accumulation and bioconcentration in the vegetative and reproductive organs of Raphanus sativus: implications for plant performance and pollination.

Several studies have found high levels of cadmium (Cd), copper (Cu), and lead (Pb) in honey bee hives located near urbanized or industrial areas. Insect herbivores and pollinators may come in contact with environmental contaminants in the leaves and flowers they forage upon in these areas. Our study quantified which of these metals are accumulated in the tissues of a common weedy plant that can serve as a route of exposure for insects. We grew Raphanus sativus (crop radish) in semi-hydroponic sand culture in the greenhouse. Plants were irrigated with nutrient solutions containing Cd, Cu, or Pb at four concentrations (control, low, medium, high). Plant performance, floral traits, and metal accumulation were measured in various vegetative and reproductive plant organs. Floral traits and flower number were unaffected by all metal treatments. Copper accumulated at the highest concentrations in flowers compared to the other two metals. Copper and Cd had the highest translocation indices, as well as higher bioconcentration factors compared to Pb, which was mostly immobile in the plant. Copper posed the highest risk due to its high mobility within the plant. In particular, accumulation of metals in leaves and flowers suggests that herbivores and pollinators visiting and foraging on these tissues may be exposed to these potentially toxic compounds.

A binomial sequential sampling plan for Bactericera cockerelli (Hemiptera: Triozidae) in Solanum lycopersicum (Solanales: Solanacea).

The tomato-potato psyllid Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) is a pest of many solanaceous plants, including tomato (Solanum lycopersicum L.) and potato (Solanum tuberosum L.). In tomato, feeding by nymphs is associated with "psyllid yellows." B. cockerelli also vectors "Candidatus Liberibacter psyllaurous," an infectious bacterium that causes "vein greening" disease. Decisions about management action are much more effective when guided by robust sampling. However, there are few previous studies of potato psyllid spatial distribution in tomato fields, and no published sequential sampling plans for the pest in tomato. We studied B. cockerelli in various tomato fields in California and used these data to generate a sequential sampling plan. We found that juvenile B. cockerelli in tomato fields exhibit an edge effect, an aggregated distribution, and individuals are primarily located on the bottom of leaves. Psyllids were concentrated in the upper segments of plants, but this changed over time. Finally, we present three binominal sequential sampling plans for managing tomato psyllids in tomato fields. These plans differed from both those for bell pepper (Capsicum annum L.) and potato, indicating that B. cockerelli needs to be sampled using crop-specific sampling plans.

Cadmium contamination triggers negative bottom-up effects on the growth and reproduction of Frankliniella occidentalis (Thysanoptera: Thripidae) without disrupting the foraging behavior of its predator, Orius sauteri (Heteroptera: Anthocoridae).

Heavy metal contaminants may influence tri-trophic interactions among plants, herbivores, and their natural enemies and affect the results of pest management practices. We examined how the widely distributed heavy metal cadmium (Cd) could modify interactions between kidney bean, Phaseolus vulgaris L., western flower thrips, Frankliniella occidentalis Pergande, and a predator, Orius sauteri (Poppius) by examining Cd effects on the feeding damage on leaves, the growth and reproduction of the thrips, and the feeding and plant location selection behaviors of predators. Leaf feeding damage was significantly reduced only at the highest Cd treatment (625 mg L-1). Survival, reproduction, and population growth of thrips decreased with the increase of Cd treatment concentration (0, 25, and 625 mg L-1). The reproduction rate of thrips from the highest Cd treatment group was reduced to less than 30% of the controls. Predator choice of plants was not impacted at the lowest level of Cd treatment (25 mg L-1) when prey were excluded, but the predators were deterred from plants treated at the high level of Cd (625 mg L-1). However, the predators responded strongly to the presence of prey, and the Cd-based deterrence was effectively eliminated when prey were added. Thus, the presence of Cd can cause a bottom-up effect on the fitness of pests without disrupting the foraging behavior of its predator. Our results provide baseline data on the toxic impacts on the pest and predator, and indicate that the ecology of the system and the biological control efficiency would be potentially impacted by high levels of Cd (625 mg L-1).

The impact of selenium on insects.

Selenium, a naturally occurring metalloid, is an essential trace element for many higher organisms, including humans. Humans primarily become exposed to selenium by ingesting food products containing trace amounts of selenium compounds. Although essential in these small amounts, selenium exhibits toxic effects at higher doses. Previous studies investigating the effects on insects of order Blattodea, Coleoptera, Diptera, Ephemeroptera, Hemiptera, Hymenoptera, Lepidoptera, Odonata, and Orthoptera revealed impacts on mortality, growth, development, and behavior. Nearly every study examining selenium toxicity has shown that insects are negatively affected by exposure to selenium in their food. However, there were no clear patterns of toxicity between insect orders or similarities between insect species within families. At this time, the potential for control will need to be determined on a species-by-species basis. We suspect that the multiple modes of action, including mutation-inducing modification of important amino acids as well as impacts on microbiome composition, influence this variability. There are relatively few studies that have examined the potential effects of selenium on beneficial insects, and the results have ranged from increased predation (a strong positive effect) to toxicity resulting in reduced population growth or even the effective elimination of the natural enemies (more common negative effects). As a result, in those pest systems where selenium use is contemplated, additional research may be necessary to ascertain if selenium use is compatible with key biological control agents. This review explores selenium as a potential insecticide and possible future directions for research.

An immune-based tool platform for in vivo cell clearance.

Immunological targeting of pathological cells has been successful in oncology and is expanding to other pathobiological contexts. Here, we present a flexible platform that allows labeling cells of interest with the surface-expressed model antigen ovalbumin (OVA), which can be eliminated via either antigen-specific T cells or newly developed OVA antibodies. We demonstrate that hepatocytes can be effectively targeted by either modality. In contrast, pro-fibrotic fibroblasts associated with pulmonary fibrosis are only eliminated by T cells in initial experiments, which reduced collagen deposition in a fibrosis model. This new experimental platform will facilitate development of immune-based approaches to clear potential pathological cell types in vivo.

Identification and impact of natural enemies of Bactericera cockerelli (Hemiptera: Triozidae) in Southern California.

Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) is a major pest of potato, (Solanum tuberosum L.), tomato (Solanum lycopersicum L.), and peppers (Capsicum spp.). The purpose of our research was to identify and determine the impact of natural enemies on B. cockerelli population dynamics. Through 2 yr of field studies (2009-2010) at four different sites and laboratory feeding tests, we identified minute pirate bug, Orius tristicolor (White) (Hemiptera: Anthocoridae); western bigeyed bug, Geocoris pallens Stål (Hemiptera:Geocoridae), and convergent lady beetle, Hippodamia convergens Guérin-Méneville (Coleoptera: Coccinellidae) as key natural enemies of B. cockerelli in southern California potatoes, tomatoes, and bell peppers. In natural enemy exclusion cage experiments in the potato crop and in American nightshade, Solanum americanum Miller, the number of B. cockerelli surviving was significantly greater in the closed cage treatments, thus confirming the affect natural enemies can have on B. cockerelli. We discuss how this information can be used in an integrated pest management program for B. cockerelli.

Risk assessment of selected insecticides on Tamarixia triozae (Hymenoptera: Eulophidae), a parasitoid of Bactericera cockerelli (Hemiptera: Trizoidae).

Tamarixia triozae (Burks) (Hymenoptera: Eulophidae) is an important parasitoid of the potato or tomato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Trizoidae), a serious pest of potato (Solanum tuberosum L.), tomato (Solanum lycopersicum L.), and other solanaceous vegetables in many countries. To produce a marketable crop, insecticides are required when B. cockerelli populations reach economically damaging levels. We evaluated 11 commonly used insecticides for their effects on T. triozae. Glass-surface residues of spinetoram, imidacloprid-cyfluthrin, abamectin, and tolfenpyrad caused 100% mortality of T. triozae in 72 h, and the leaf residue of spinetoram was extremely toxic to T. triozae adults; even 15-d-old residues caused 100% mortality. Cyantraniliprole, fenpyroximate, pymetrozine, spirotetramat, spiromesifen, and chenopodium oil did not cause significant mortality in either glass surface or leaf-residue bioassays. Ingestion of spinetoram, abamectin, and imidacloprid+cyfluthrin (Leverage) by the adults resulted in 100% mortality in 12 h, and tolfenpyrad, 75.0% mortality in 12 h; whereas chenopodium oil and pymetrozine showed moderate effects on adult survival. Ingestion of abamectin, imidacloprid-cyfluthrin, and spinetoram killed all adults in the first day of treatment, whereas female adults in the treatment of pymetrozine lived 80.8 d, which was similar to those in the control. Ingestion of abamectin, imidacloprid-cyfluthrin, chenopodium oil, and spinetoram killed all male adults in the first day, whereas ingestion of other insecticides did not cause significant mortality, but reduced percent parasitism. Abamectin, imidacloprid-cyfluthrin, and spinetoram had the most deleterious effects on T. triozae, and have the least potential for use in integrated control programs using this parasitoid.

Modeling and validation of oviposition by a polyphagous insect pest as a function of temperature and host plant species.

Modeling oviposition as a function of female insect age, temperature, and host plant suitability may provide valuable insight into insect population growth of polyphagous insect pests at a landscape level. In this study, we quantified oviposition by beet leafhoppers, Circulifer (= Neoaliturus) tenellus (Baker) (Hemiptera: Cicadellidae), on four common non-agricultural host plant species [Erodium cicutarium (L.) L'Hér. (Geraniaceae), Kochia scoparia (L.) Schrader (Amaranthaceae), Plantago ovata Forsskál (Plantaginaceae), and Salsola tragus L. (Amaranthaceae)] at two constant temperature conditions. Additionally, temperature-based oviposition models for each host plant species were validated, under semi-field and greenhouse conditions. We found that K. scoparia was the most suitable host plant, and optimal temperature for oviposition was estimated to be 30.6°C. Accordingly, beet leafhoppers appear to be well-adapted to high-temperature conditions, so increasing temperatures due to climate change may favor population growth in non-agricultural areas. Maximum total fecundity (Rm) was used as an indicator of relative suitability of host plants. S. tragus has been considered an important non-agricultural host plant, however, we found that S. tragus and E. cicutarium have lower Rm compared to K. scoparia and P. ovata. The combination of detailed experimental oviposition bioassays, modeling, and model validation is considered widely relevant and applicable to host plant assessments and modeling of population dynamics of other polyphagous insect pests.

Insect vector manipulation by a plant virus and simulation modeling of its potential impact on crop infection.

There is widespread evidence of plant viruses manipulating behavior of their insect vectors as a strategy to maximize infection of plants. Often, plant viruses and their insect vectors have multiple potential host plant species, and these may not overlap entirely. Moreover, insect vectors may not prefer plant species to which plant viruses are well-adapted. In such cases, can plant viruses manipulate their insect vectors to preferentially feed and oviposit on plant species, which are suitable for viral propagation but less suitable for themselves? To address this question, we conducted dual- and no-choice feeding studies (number and duration of probing events) and oviposition studies with non-viruliferous and viruliferous [carrying beet curly top virus (BCTV)] beet leafhoppers [Circulifer tenellus (Baker)] on three plant species: barley (Hordeum vulgare L.), ribwort plantain (Plantago lanceolata L.), and tomato (Solanum lycopersicum L.). Barley is not a host of BCTV, whereas ribwort plantain and tomato are susceptible to BCTV infection and develop a symptomless infection and severe curly top symptoms, respectively. Ribwort plantain plants can be used to maintain beet leafhopper colonies for multiple generations (suitable), whereas tomato plants cannot be used to maintain beet leafhopper colonies (unsuitable). Based on dual- and no-choice experiments, we demonstrated that BCTV appears to manipulate probing preference and behavior by beet leafhoppers, whereas there was no significant difference in oviposition preference. Simulation modeling predicted that BCTV infection rates would to be higher in tomato fields with barley compared with ribwort plantain as a trap crop. Simulation model results supported the hypothesis that manipulation of probing preference and behavior may increase BCTV infection in tomato fields. Results presented were based on the BCTV-beet leafhopper pathosystem, but the approach taken (combination of experimental studies with complementary simulation modeling) is widely applicable and relevant to other insect-vectored plant pathogen systems involving multiple plant species.

Effects of insecticides on behavior of adult Bactericera cockerelli (Hemiptera: Triozidae) and transmission of Candidatus Liberibacter psyllaurous.

The potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), is a serious pest of potatoes (Solanum tuberosum L.) that can cause yield loss by direct feeding on crop plants and by vectoring a bacterial pathogen, Candidatus Liberibacer psyllaurous. Current pest management practices rely on the use of insecticides to control the potato psyllid to lower disease incidences and increase yields. Although many studies have focused on the mortality that insecticides can cause on potato psyllid populations, little is known regarding the behavioral responses of the potato psyllid to insecticides or whether insecticides can decrease pathogen transmission. Thus, the objectives of this study were to determine the effects of insecticides on adult potato psyllid behaviors, the residual effects of insecticides on potato psyllid behaviors over time, and effects of these insecticides on Ca. L. psyllaurous transmission. Insecticides tested included imidacloprid, kaolin particle film, horticultural spray oil, abamectin, and pymetrozine. All insecticides significantly reduced probing durations and increased the amount of time adult psyllids spent off the leaflets, suggesting that these chemicals may be deterrents to feeding as well as repellents. Nonfeeding behaviors such as tasting, resting, and cleaning showed variable relationships with the different insecticide treatments over time. The insecticides imidacloprid and abamectin significantly lowered transmission of Ca. L. psyllaurous compared with untreated controls. The implications of our results for the selection of insecticides useful for an integrated pest management program for potato psyllid control are discussed.

Inhibition of longevity regulator PAPP-A modulates tissue homeostasis via restraint of mesenchymal stromal cells.

Pregnancy-associated plasma protein-A (PAPP-A) is a secreted metalloprotease that increases insulin-like growth factor (IGF) availability by cleaving IGF-binding proteins. Reduced IGF signaling extends longevity in multiple species, and consistent with this, PAPP-A deletion extends lifespan and healthspan; however, the mechanism remains unclear. To clarify PAPP-A's role, we developed a PAPP-A neutralizing antibody and treated adult mice with it. Transcriptomic profiling across tissues showed that anti-PAPP-A reduced IGF signaling and extracellular matrix (ECM) gene expression system wide. The greatest reduction in IGF signaling occurred in the bone marrow, where we found reduced bone, marrow adiposity, and myelopoiesis. These diverse effects led us to search for unifying mechanisms. We identified mesenchymal stromal cells (MSCs) as the source of PAPP-A in bone marrow and primary responders to PAPP-A inhibition. Mice treated with anti-PAPP-A had reduced IGF signaling in MSCs and dramatically decreased MSC number. As MSCs are (1) a major source of ECM and the progenitors of ECM-producing fibroblasts, (2) the originating source of adult bone, (3) regulators of marrow adiposity, and (4) an essential component of the hematopoietic niche, our data suggest that PAPP-A modulates bone marrow homeostasis by potentiating the number and activity of MSCs. We found that MSC-like cells are the major source of PAPP-A in other tissues also, suggesting that reduced MSC-like cell activity drives the system-wide reduction in ECM gene expression due to PAPP-A inhibition. Dysregulated ECM production is associated with aging and drives age-related diseases, and thus, this may be a mechanism by which PAPP-A deficiency enhances longevity.

Joint effects of cadmium and copper on Apis mellifera forgers and larvae.

Honey bees (Apis mellifera L.) are important ecological and agricultural resources. They are among the most widely available pollinators and provide products as well as services. Unfortunately, honey bee populations are susceptible to several environmental threats, including heavy metal exposure. Honey bees can be exposed to heavy metals when foraging on contaminated honey and pollen resources, and in some cases by airborne exposure. We studied the joint acute and chronic effects of cadmium (Cd) and copper (Cu) on A. mellifera. A 1:1 solution of the two heavy metals increased larval developmental duration and the mortality of both larvae and foragers in a dose-dependent way, decreased forager feeding, increased body metal burdens, and disrupted the sucrose response behavior of foragers. In combination, Cd and Cu demonstrated a weakly synergistic effect on foragers, but for larvae an initially antagonistic effect at low doses changed to strongly synergistic response at higher concentrations. The sucrose response threshold of foragers decreased significantly when they were dosed with increasing concentrations of the metal mixtures. Overall, the fitness of honey bee larvae and foragers is detrimentally affected when these metals co-occur.