Variation in Pesticide Toxicity in the Western Honey Bee (Apis mellifera) Associated with Consuming Phytochemically Different Monofloral Honeys.

Insecticide toxicity to insect herbivores has long been known to vary across different host plants; this phenomenon has been widely documented in both foliage-feeders and sap-feeders. Species-specific phytochemical content of hostplant tissues is assumed to determine the pattern of induction of insect enzymes that detoxify insecticides, but specific phytochemicals have rarely been linked to host plant-associated variation in pesticide toxicity. Moreover, no studies to date have examined the effects of nectar source identity and phytochemical composition on the toxicity of insecticides to pollinators. In this study, we compared LD50 values for the insecticide bifenthrin, a frequent contaminant of nectar and pollen in agroecosystems, in the western honey bee, Apis mellifera, consuming three phytochemically different monofloral honeys: Nyssa ogeche (tupelo), Robinia pseudoacacia (black locust), and Fagopyrum esculentum (buckwheat). We found that bifenthrin toxicity (LD50) values for honey bees across different honey diets is linked to their species-specific phytochemical content. The profiles of phenolic acids and flavonoids of buckwheat and locust honeys are richer than is the profile of tupelo honey, with buckwheat honey containing the highest total content of phytochemicals and associated with the highest bifenthrin LD50 in honey bees. The vector fitting in the ordination analysis revealed positive correlations between LD50 values and two honey phytochemical richness estimates, Chao1 and Abundance-based Coverage Estimator (ACE). These findings suggest unequal effects among different phytochemicals, consistent with the interpretation that certain compounds, including ones that are rare, may have a more pronounced effect in mitigating pesticide toxicity.

No buzz for bees: Media coverage of pollinator decline.

Although widespread declines in insect biomass and diversity are increasing concerns within the scientific community, it remains unclear whether attention to pollinator declines has also increased within information sources serving the general public. Examining patterns of journalistic attention to the pollinator population crisis can also inform efforts to raise awareness about the importance of declines of insect species providing ecosystem services beyond pollination. We used the Global News Index developed by the Cline Center for Advanced Social Research at the University of Illinois at Urbana-Champaign to track news attention to pollinator topics in nearly 25 million news items published by two American national newspapers and four international wire services over the past four decades. We found vanishingly low levels of attention to pollinator population topics relative to coverage of climate change, which we use as a comparison topic. In the most recent subset of ∼10 million stories published from 2007 to 2019, 1.39% (137,086 stories) refer to climate change/global warming while only 0.02% (1,780) refer to pollinator populations in all contexts, and just 0.007% (679) refer to pollinator declines. Substantial increases in news attention were detectable only in US national newspapers. We also find that, while climate change stories appear primarily in newspaper "front sections," pollinator population stories remain largely marginalized in "science" and "back section" reports. At the same time, news reports about pollinator populations increasingly link the issue to climate change, which might ultimately help raise public awareness to effect needed policy changes.

MOF-Based Biosensors for the Detection of Carcinoembryonic Antigen: A Concise Review.

Cancer has been considered one of the most serious diseases in recent decades. Early diagnosis of cancer is a crucial step for expedited treatment. Ideally, detection of cancer biomarkers, which are usually elevated because of cancer, is the most straightforward approach to detecting cancer. Among these biomarkers, the carcinoembryonic antigen (CEA) is considered one of the most important tumor markers for colorectal cancer. The CEA has also been recognized as a biomarker for other types of cancers, including breast, gastric, ovarian, pancreatic, and lung cancers. Typically, conventional CEA testing depends on immunoassay approaches, which are known to be complex, highly expensive, and time consuming. Accordingly, various types of biosensors have been designed for the detection of cancer biomarkers. The main prerequisites of these biosensors are high sensitivity, fast response, and low cost. Many nanostructures have been involved in the design of biosensors, such as nanoparticles of certain metals and metal oxides that are further functionalized to contribute to the sensing of the biomarkers. Alternatively, metal organic frameworks (MOFs), which are extended crystalline structures comprising metal clusters surrounded by organic linkers, have been shown to be highly promising for the development of biosensors. The 3D structure of MOFs results in a combination of high surface area and high interconnected porosity, which are believed to facilitate their function in the design of a biosensor. This review briefly classifies and describes MOF-based biosensor trials that have been published recently for the aim of detecting CEA.

EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma.

Juvenile open-angle glaucoma (JOAG) is a severe type of glaucoma with onset before age 40 and dominant inheritance. Using exome sequencing we identified 3 independent families from the Philippines with novel EFEMP1 variants (c.238A>T, p.Asn80Tyr; c.1480T>C, p.Ter494Glnext*29; and c.1429C>T, p.Arg477Cys) co-segregating with disease. Affected variant carriers (N = 34) exhibited severe disease with average age of onset of 16 years and with 76% developing blindness. To investigate functional effects, we transfected COS7 cells with vectors expressing the three novel EFEMP1 variants and showed that all three variants found in JOAG patients caused significant intracellular protein aggregation and retention compared to wild type and also compared to EFEMP1 variants associated with other ocular phenotypes including an early-onset form of macular degeneration, Malattia Leventinese/Doyne's Honeycomb retinal dystrophy. These results suggest that rare EFEMP1 coding variants can cause JOAG through a mechanism involving protein aggregation and retention, and that the extent of intracellular retention correlates with disease phenotype. This is the first report of EFEMP1 variants causing JOAG, expanding the EFEMP1 disease spectrum. Our results suggest that EFEMP1 mutations appear to be a relatively common cause of JOAG in Filipino families, an ethnically diverse population.

Degree of Dietary Specialization on Furanocoumarin-Containing Hostplants in a Newly Invasive Web Building Caterpillar.

The genus Depressaria (Lepidoptera: Depressariidae) mostly comprises specialist herbivores with varying capacity for detoxification of defensive phytochemistry. Depressaria depressana, a Eurasian moth recently introduced into North America, is a family-level specialist of the Apiaceae, whose hosts include more than a dozen species in multiple tribes; Depressaria radiella is a super-specialist of Eurasian origin that feeds exclusively on species in the genera Pastinaca and Heracleum throughout its native and introduced range. In eastern North America, it feeds upon Pastinaca sativa, an invasive European species, and Heracleum maximum, a native species. We determined whether differences in furanocoumarin metabolism exist between D. depressana and two isolated populations of D. radiella, feeding exclusively on either P. sativa or H. maximum. We also compared gravimetric estimates of feeding efficiency to assess D. depressana larval performance on different diets. Both populations of D. radiella metabolized furanocoumarins at a greater rate than D. depressana. Although there was no difference in rates of metabolism of linear furanocoumarins in the two populations of D. radiella, individuals collected from H. maximum metabolized angular furanocoumarins more rapidly. The gravimetric assessments of feeding efficiencies revealed that D. depressana exhibited highest efficiencies consuming Daucus carota; moreover, this species survived to pupation consuming fruits of Zizia aurea, an apiaceous species native to North America. Our preliminary phylogenetic analysis, building on an earlier morphological analysis, incorporates mitochondrial cytochrome oxidase subunit 1 data from the BOLD database and revealed that the presence or absence of furanocoumarins is not a strong predictor of species-level evolution in Depressaria.

Defining the decision-to-delivery interval at caesarean section: narrative literature review and proposal for standardisation.

The decision-to-delivery interval is a widely used term at non-elective caesarean section. While the definition may appear self-evident, there is no universally agreed consensus about when this period begins and ends. We reviewed the literature for original research utilising the terms 'decision-to-delivery', 'decision-to-incision' or 'incision-to-delivery' and examined definitions used for decision, delivery, incision, as well as any additional time intervals that were assessed. Our analysis demonstrated an inconsistent non-standardised approach to defining these intervals, which might have clinical practice and medicolegal ramifications. We propose that the decision-to-delivery interval should be defined as follows: the interval between the time at which the senior obstetrician makes the decision that a caesarean section is required and the time at which the fetus (or first fetus in the case of multiples) is delivered. The decision time should ideally be recorded contemporaneously in the medical notes or partogram.

Honey as a Functional Food for Apis mellifera.

Although nectar is consumed, primarily as a supplemental food, by a broad range of insects spanning at least five orders, it is processed and stored by only a small number of species, most of which are bees and wasps in the superfamily Apoidea. Within this group, Apis mellifera has evolved remarkable adaptations facilitating nectar processing and storage; in doing so, this species utilizes the end product, honey, for diverse functions with few if any equivalents in other phytophagous insects. Honey and its phytochemical constituents, some of which likely derive from propolis, have functional significance in protecting honey bees against microbial pathogens, toxins, and cold stress, as well as in regulating development and adult longevity. The distinctive properties of A. mellifera honey appear to have arisen in multiple ways, including genome modification; partnerships with microbial symbionts; and evolution of specialized behaviors, including foraging for substances other than nectar. That honey making by A. mellifera involves incorporation of exogenous material other than nectar, as well as endogenous products such as antimicrobial peptides and royal jelly, suggests that regarding honey as little more than a source of carbohydrates for bees is a concept in need of revision.

ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer.

BACKGROUND: Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥ third-line treatment of mNSCLC. PATIENTS AND METHODS: ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC <25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B). RESULTS: Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (CI), 0.42-0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49-1.04)]. Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61-1.05); P = 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59-1.01); P = 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; study B). CONCLUSIONS: In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC <25%). Safety profiles were consistent with previous studies. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02352948.

Factors Associated with Variation in Cuticular Hydrocarbon Profiles in the Navel Orangeworm, Amyelois transitella (Lepidoptera: Pyralidae).

Cuticular hydrocarbons (CHCs) are the main components of the epicuticular wax layer that in many insects functions as a barrier against desiccation. CHCs also play many other roles, including serving as sex pheromones, kairomones, primer pheromones, and colony-, caste-, species- and sex-recognition signals. In insects, CHC profiles can vary depending upon age, species, sex, and strain. Understanding factors associated with variation in hydrocarbon profiles is important for identifying potential vulnerabilities relating to pest ecology and life histories and for developing tools for pest monitoring and management strategies. In this study, we assessed potential sources of variation in CHC profiles in the navel orangeworm Amyelois transitella (Walker) (Lepidoptera: Pyralidae), an economically important pest of nut crops in California. Using coupled gas chromatography-mass spectrometry, we characterized and compared CHC profiles between adults of pyrethroid-resistant (R347) and susceptible (ALMOND) strains. We further compared CHC profiles from adults differing in age (1, 3, 5, and 7 d post-eclosion) and sex. Hydrocarbon profiles comprised 47 different CHCs in detectable quantities that ranged from C17 to C43 in chain length and included straight-chain alkanes and a variety of mono-, di-, and tri-methylalkanes. Adults from resistant populations had greater quantities of CHCs in total than those from susceptible strains, but relative quantities of individual components were similar. The six most abundant compounds were n-pentacosane, n-heptacosane, n-nonacosane, n-hentriacontane, 11,25 + 13,23 + 15,21-dimethylpentatriacontane, and 13,23 + 11,25 + 9,17-dimethylheptatriacontane. Post-eclosion, total CHCs increased with adult age, with males producing greater quantities than females at all ages. Our results show that CHC profiles vary depending on age, sex, and strain and suggest that CHC profiles may be useful as biomarkers to differentiate between insecticide- resistant and susceptible populations.

Author Correction: Factors Associated with Variation in Cuticular Hydrocarbon Profiles in the Navel Orangeworm, Amyelois transitella (Lepidoptera: Pyralidae).

The original version of this article unfortunately contained a mistake. When filing the final publication details, we failed to include the following statement in our Acknowledgments paragraph: We thank the Almond Board of California for research funding.

Disruption of quercetin metabolism by fungicide affects energy production in honey bees (Apis mellifera).

Cytochrome P450 monooxygenases (P450) in the honey bee, Apis mellifera, detoxify phytochemicals in honey and pollen. The flavonol quercetin is found ubiquitously and abundantly in pollen and frequently at lower concentrations in honey. Worker jelly consumed during the first 3 d of larval development typically contains flavonols at very low levels, however. RNA-Seq analysis of gene expression in neonates reared for three days on diets with and without quercetin revealed that, in addition to up-regulating multiple detoxifying P450 genes, quercetin is a negative transcriptional regulator of mitochondrion-related nuclear genes and genes encoding subunits of complexes I, III, IV, and V in the oxidative phosphorylation pathway. Thus, a consequence of inefficient metabolism of this phytochemical may be compromised energy production. Several P450s metabolize quercetin in adult workers. Docking in silico of 121 pesticide contaminants of American hives into the active pocket of CYP9Q1, a broadly substrate-specific P450 with high quercetin-metabolizing activity, identified six triazole fungicides, all fungal P450 inhibitors, that dock in the catalytic site. In adults fed combinations of quercetin and the triazole myclobutanil, the expression of five of six mitochondrion-related nuclear genes was down-regulated. Midgut metabolism assays verified that adult bees consuming quercetin with myclobutanil metabolized less quercetin and produced less thoracic ATP, the energy source for flight muscles. Although fungicides lack acute toxicity, they may influence bee health by interfering with quercetin detoxification, thereby compromising mitochondrial regeneration and ATP production. Thus, agricultural use of triazole fungicides may put bees at risk of being unable to extract sufficient energy from their natural food.

Fungicide suppression of flight performance in the honeybee (Apis mellifera) and its amelioration by quercetin.

As a managed agricultural pollinator, the western honeybee Apis mellifera frequently encounters agrochemicals as contaminants of nectar and pollen. One such contaminant, the fungicide boscalid, is applied at bloom in orchards for fungal floral pathogen control. As an inhibitor of complex II in the mitochondrial electron transport chain of fungi, boscalid can potentially interfere with high energy-demanding activities of bees, including flight. We designed an indoor flight treadmill to evaluate impacts of ingesting boscalid and/or quercetin, a ubiquitous phytochemical in bee food that also affects mitochondrial respiration. Boscalid reduced the wingbeat frequencies of foragers during flight but did not alter the duration of flight. At the colony level, boscalid ingestion may thereby affect overall health by reducing forager efficiency. The consumption of quercetin, by contrast, led to higher adenosine triphosphate levels in flight muscles and a higher wingbeat frequency. Consuming the two compounds together increased wingbeat frequency, demonstrating a hitherto unrecognized mechanism by which dietary phytochemicals may act to ameliorate toxic effects of pesticides to promote honeybee health. In carrying out this work, we also introduce two methodological improvements for use in testing for pesticide effects on flight capacity-a 'force-feeding' to standardize flight fuel supply and a novel indoor flight treadmill.

Honey Bees and Environmental Stress: Toxicologic Pathology of a Superorganism.

As a eusocial species, Apis mellifera, the European honey bee, is effectively a superorganism-a group of genetically related individuals functioning as a collective unit. Because the unit of selection is the colony and not the individual, standard methods for assessing toxicologic pathology can miss colony-level responses to stress. For over a decade, US populations of honeybees have experienced severe annual losses attributed to a variety of environmental stressors varying temporally and geographically; differentiating among those stressors is accordingly a high priority. Social interactions among individuals in this social species, however, mean that the "footprint" of stressors such as pesticides, phytochemicals, pathogens, and parasites may be most discernible in individuals that did not themselves directly encounter the stressor. For example, neurotoxic effects of pesticides on nurse bees may impair their behavioral responses to queen-destined larvae, which may then emerge as adults with altered anatomy or physiology. Similarly, pesticide-induced size alterations in nurse hypopharyngeal glands, which produce royal jelly, the exclusive food of larval and adult queens, may disproportionately affect the queen's (and thus colony) health. Thus, evaluating toxicologic pathology in the honeybee requires a new perspective and development of assays that preserve the social context that ultimately determines colony health.

Mediation of Impacts of Elevated CO2 and Light Environment on Arabidopsis thaliana (L.) Chemical Defense against Insect Herbivory Via Photosynthesis.

Elevated CO2 alters C3 plant tolerance to insect herbivory, as well as the induction kinetics of defense hormones salicylic acid (SA) and jasmonic acid (JA), but the underlying physiological mechanism causing this response is not well understood. In principle, SA could be induced under elevated CO2 by reactive oxygen signals generated in photosynthesis, ultimately influencing chemical defense. To test whether the effects of elevated CO2 on C3 plant chemical defense against herbivorous insects are modulated by photosynthesis, Arabidopsis thaliana var. Col-0 plants were grown in two 2 × 2 × 2 nested factorial combinations of ambient (400 ppm) and elevated (800 ppm) CO2, and two dimensions of light regimes comprising intensity ('mild' 150 µmol E m-2 s-1 vs. 'low' light, 75 µmol E m-2 s-1) and periodicity ('continuous', 150 µmol E m-2 s-1 vs. 'dynamic', in which lights were turned off, then on, for 15 min every 2 h). Plants were challenged with herbivore damage from third instar Trichoplusia ni (cabbage looper). Consistent with experimental predictions, elevated CO2 interacted with light as well as herbivory to induce foliar concentration of SA, while JA was suppressed. Under dynamic light, foliar content of total glucosinolates was reduced. Under combination of elevated CO2 and dynamic light, T. ni removed significantly more leaf tissue relative to control plants. The observations that CO2 and light interactively modulate defense against T. ni in A. thaliana provide an empirical argument for a role of photosynthesis in C3 plant chemical defense.