Search

Summary Background COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. Methods Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. Findings In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. Interpretation Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. Funding Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council. more...

Purpose Fellows in Pediatric Surgery need to learn to manage a variety of gynecologic conditions. We completed a needs assessment of Pediatric Surgery training programs to inform development of a standardized gynecology curriculum. Methods A survey was sent to Program Directors of Canadian Pediatric Surgery training programs with 27 questions that focused on the fellowship program, surgical practice, and trainee exposure to pediatric gynecology, and how the envision a standardized gynecology curriculum. Results Six of eight Program Directors responded. All respondents had treated ovarian-related conditions and genital injuries in the past 5 years, and most felt trainees received adequate training in managing these conditions. Most respondents felt trainees had minimal or inadequate training in imperforate hymens, Mullerian anomalies, vulvar abscesses, vaginal foreign bodies, and labial adhesions. Program Directors currently allot an average of 3.5 h to delivering the gynecology objectives. All Program Directors expressed interest in a formal gynecology curriculum delivered through some combination of case-based teaching and/or simulation. Conclusion There is a need for a standardized gynecology curriculum for Pediatric Surgery trainees. Most Pediatric Surgeons will manage gynecological conditions as part of their practice and current Program Directors feel that training is inadequate for a number of gynecological conditions. Type of Study Observational Cross-Sectional Study. Level of Evidence Level IV. more...

The Wittig reaction to synthesize olefins is a very attractive method in organic synthesis. Recently, this methodology has been achieved utilizing simple metal catalysts and diazo compounds in addition to a phosphine and an aldehyde. The following work investigates the use of a variety of metallophthalocyanines (MPc’s) to catalyze Wittig-like reactions from ethyldiazoacetate. We also examine the influence of substitution on the aromatic ring of the aldehyde as well as various phosphines, arsines and antimony complexes. We have been able to exclusively synthesize the trans-olefins in excellent yields in short periods of time (1 h). more...

Climatic requirements of natural enemies have important implications for predicting the outcome of classical biological control programs. A five year study (2011–2015) investigated the ectoparasitoid community of the oilseed rape pest Ceutorhynchus obstrictus (Coleoptera: Curculionidae), in different climate zones across Europe to better understand the distribution, abundance, phenology and thermal requirements of Trichomalus perfectus and Mesopolobus morys (Hymenoptera: Pteromalidae). Data generated were then used to develop bioclimatic models to predict the suitability and potential distribution of each species if introduced into North America for biological control of C. obstrictus. Findings indicated that, although T. perfectus and M. morys occupy the same feeding niche and overlap temporally, there are clear geographic differences in abundance. Trichomalus perfectus appears to be a ‘northern’ maritime species, whereas M. morys is likely a ‘southern’, continental species. If introduced, it was predicted that both species would establish in canola growing regions of North America, although climatic conditions appear to be less favourable for T. perfectus than M. morys. This study showed that variation in regional distributions may occur and these are likely based on differing tolerance to climatic conditions. Understanding these tolerances can enhance precision of ecological niche models that predict potential distributions of parasitoids for introduction as candidate biological control agents. Furthermore, the work reported here provides a basis for future research to determine if climate change may favour species such as M. morys that are adapted to warmer summer conditions. more...

Using heme entrapped in recombinant silk films, we have produced 3rd generation biosensors, which allow direct electron transfer from the heme center to an electrode avoiding the need for electron mediators. Here, we demonstrate the use of these heme-silk films for the detection of nitric oxide (NO) at nanomolar levels in the presence and absence of oxygen. The sensor was prepared by drop-casting a silk solution on a glassy carbon electrode modified with multiwalled carbon nanotubes (MWCNT) followed by infusion with heme. The sensor was characterized by cyclic voltammetry and showed well defined and reversible Fe+/ Fe3+ redox couple activity, with NO detection by oxidation at potentials above +0.45V or reduction at potentials below - 0.7V. Evaluation of the effect of pH on the sensor response to NO reduction indicated a maximum response at pH 3. The sensor showed good linearity in the concentration range from 19 to 190nM (R2 = 0.99) with a detection limit of 2nM. The sensor had excellent selectivity towards NO with no or negligible interference from oxygen, nitrite, nitrate, dopamine and ascorbic acid and retained 86% of response after 2 months of operation and storage at room temperature. more...

The metabolite itaconate plays a critical role in modulating inflammatory responses among macrophages infected with intracellular pathogens. However, the ability of itaconate to influence developing T cells responses is poorly understood. To determine if itaconate contributes to the quality of T cell mediated immunity against intracellular infection, we used Francisella tularensis as a model of vaccine induced immunity. Following vaccination with F. tularensis live vaccine strain, itaconate deficient mice (ACOD KO) had a prolonged primary infection but were more resistant to secondary infection with virulent F. tularensis relative to wild type controls. Improved resistance to secondary challenge was associated with both increased numbers and effector function of CD4 more...

Purpose Sexual activity is a normative part of adolescent development, yet early sexual debut and sex with multiple partners undermine health and well-being. Both structural (e.g., poverty) and social (e.g., norms) characteristics of neighborhoods shape sexual risk taking, yet scholarship remains focused on urban areas. Thus, this study explores sexually permissive attitudes and sexual risk taking across a wider expanse of neighborhood types. Methods Among 8,337 nonsexually active respondents in Wave I (1994–1995 [ages 11–18]) of the National Longitudinal Study of Adolescent to Adult Health (Add Health), a hierarchical linear model and a hierarchical generalized linear model were used to estimate the effect of neighborhood type and permissive sexual climate on youths' sexual debut, age at debut, and lifetime number of sexual partners by Wave III (2001–2002 [ages 18–26]), controlling for individual, familial, and peer factors. Results Sexual climates varied in overall permissiveness and internal consistency both across and within neighborhood types and were linked to increased sexual risk taking. Compared with youth from upper middle class white suburbs, the odds of sexual debut and the number of partners were highest among youth from rural (black and white) neighborhoods; youth from almost all other neighborhood types initiated sex earlier. Conclusions Early sexual debut in adolescence is a public health issue with immediate and long-term implications. Adolescence unfolds in neighborhood environments, the characteristics of which may spur youth into such risk taking. Continued scholarship on sexual risks should consider further variations in the geographic distributions of such risks to investigate more fully their consequences. more...

Sequence-definable polymers are seen as a prerequisite for design of future materials, with many polymer scientists regarding such polymers as the holy grail of polymer science. Recombinant proteins are sequence-defined polymers. Proteins are dictated by DNA templates and therefore the sequence of amino acids in a protein is defined, and molecular biology provides tools that allow redesign of the DNA as required. Despite this advantage, proteins are underrepresented in materials science. In this publication we investigate the advantages and limitations of using proteins as templates for rational design of new materials. more...

Francisella tularensis subsp. tularensis strain SchuS4 (Ftt) is a highly virulent intracellular bacterium. Inhalation of 10 or fewer organisms results in an acute and potentially lethal disease called pneumonic tularemia. Ftt infections occur naturally in the U.S. and Ftt was developed as a bioweapon. Thus, there is a need for vaccines that protect against this deadly pathogen. Although a live vaccine strain of Francisella tularensis (LVS) exists, LVS fails to generate long-lived protective immunity against modest challenge doses of Ftt. We recently identified an important role for high avidity CD4+ T cells in short-term protection and hypothesized that expanding this pool of cells would improve overall vaccine efficacy with regard to longevity and challenge dose. In support of our hypothesis, application of a prime/boost vaccination strategy increased the pool of high avidity CD4+ T cells which correlated with improved survival following challenge with either increased doses of virulent Ftt or at late time points after vaccination. In summary, we demonstrate that both epitope selection and vaccination strategies that expand antigen-specific T cells correlate with superior immunity to Ftt as measured by survival. more...

Summary Resolution of infection results in development of trained innate immunity which is typically beneficial for defense against unrelated secondary infection. Epigenetic changes including modification of histones via binding of various polar metabolites underlie the establishment of trained innate immunity. Therefore, host metabolism and this response are intimately linked. However, little is known regarding the influence of lipids on the development and function of trained immunity. Utilizing two models of pulmonary bacterial infection combined with multi-omic approaches, we identified persistent, pathogen-specific changes to the lung lipidome that correlated with differences in the trained immune response against a third unrelated pathogen. Further, we establish the specific cellular populations in the lung that contribute to this altered lipidome. Together these results expand our understanding of the pulmonary trained innate immune response and the contributions of host lipids in informing that response., Graphical abstract, Highlights • Pathogens exert differential effects on pulmonary efferocytosis post-infection • Differences in efferocytosis are mediated by macrophage subsets • Unique immune lipid mediator milieus are linked to these macrophage subsets • Changes in the lipid landscape impact trained immunity to an unrelated infection, Biological sciences; Immunity; Genomics; Lipidomics more...

Drivers may modulate their secondary behavior based on roadway or driving demand, but there is little research capturing secondary behaviors in a range of driving situations among a large sample of drivers on actual roadways. Weekday daytime and nighttime roadside observations were conducted of drivers traveling in free-flowing traffic on a straightaway, in a roundabout, and when moving or stopped at a signalized intersection on the same roadway in four Northern Virginia communities. The presence of 12 secondary behaviors were noted for each of the 16,556 drivers observed. Overall, 23% of drivers observed were engaged in some kind of secondary behavior. The most common secondary behaviors were holding (5.1%) or talking on (4.2%) a hand-held cellphone, eating or drinking (3.1%), and talking or singing with a passenger (2.7%). Based on logistic regression analysis, the prevalence of any kind of secondary behavior and of more manually demanding behaviors, like manipulating a hand-held cellphone and eating or drinking, was highest among drivers stopped at red lights and lowest among drivers in roundabouts. Other factors also influenced the prevalence of driver secondary behavior. Drivers were more likely to be eating or drinking and less likely to be talking on a handheld phone in the morning than at others time of the day. Drivers estimated to be 60 and older were least likely to be engaged in any secondary behavior, but drivers younger than 20 and drivers 20–59 years old were equally likely. Drivers with and without passengers were equally likely to be engaged in any secondary behavior, but drivers with passengers were most likely to be talking or singing with the passengers, whereas drivers without passengers were most likely to be eating or drinking or holding, talking on, or manipulating hand-held phones. The current findings in combination with past research suggest that drivers may engage in secondary behaviors when perceived driving demand is reduced, and that roadway demand and contextual variables are important factors to consider when studying driver secondary behavior. more...

Aims To evaluate the performance of the RETeval device, a handheld instrument using flicker electroretinography (ERG) and pupillography on undilated subjects with diabetes, to detect vision-threatening diabetic retinopathy (VTDR). Methods Performance was measured using a cross-sectional, single armed, non-interventional, multi-site study with Early Treatment Diabetic Retinopathy Study 7-standard field, stereo, color fundus photography as the gold standard. The 468 subjects were randomized to a calibration phase (80%), whose ERG and pupillary waveforms were used to formulate an equation correlating with the presence of VTDR, and a validation phase (20%), used to independently validate that equation. The primary outcome was the prevalence-corrected area under the receiver operating characteristic (ROC) curve for the detection of VTDR. Results The area under the ROC curve was 0.86 for VTDR. With a sensitivity of 83%, the specificity was 78% and the negative predictive value was 99%. The average testing time was 2.3 min. Conclusions With a VTDR prevalence similar to that in the US, the RETeval device will identify about 75% of the population as not having VTDR with 99% accuracy. The device is simple to use, does not require pupil dilation, and has a short testing time. more...

Halyomorpha halys (Hemiptera: Pentatomidae) is an emerging pest which established in Ontario, Canada, in 2012. Halyomporpha halys overwinters in anthropogenic structures as an adult. We investigated seasonal variation in the cold tolerance, water balance, and energetics of H. halys in southwestern Ontario. We also induced diapause in laboratory-reared animals with short daylength at permissive temperatures and compared cold tolerance, water balance, energetics, and metabolism and gas exchange between diapausing and non-diapausing individuals. Halyomorpha halys that overwintered outside in Ontario all died, but most of those that overwintered in sheltered habitats survived. We confirm that overwintering H. halys are chill-susceptible. Over winter, Ontario H. halys depressed their supercooling point to c. −15.4 °C, and 50% survived a 1 h exposure to −17.5 °C. They reduce water loss rates over winter, and do not appear to significantly consume lipid or carbohydrate reserves to a level that might cause starvation. Overall, it appears that H. halys is dependent on built structures and other buffered microhabitats to successfully overwinter in Ontario. Laboratory-reared diapausing H. halys have lower supercooling points than their non-diapausing counterparts, but LT50 is not enhanced by diapause induction. Diapausing H. halys survive desiccating conditions for 3–4 times longer than those not in diapause, through decreases in both respiratory and cuticular water loss. Diapausing H. halys do not appear to accumulate any more lipid or carbohydrate than those not in diapause, but do have lower metabolic rates, and are slightly more likely to exhibit discontinuous gas exchange. more...

Highlights • We combined four surveillance networks of HIV/AIDS monitoring in Brazil. • We used an age-structured deterministic model to infer HIV incidence. • By 2001 a second wave of HIV infections was occurring in Brazil. • There were persistent differences in linkage to care by sex. • Of 838,000 people living with HIV by 2015, 80% were diagnosed and reported., Emerging evidence suggests that HIV incidence rates in Brazil, particularly among men, may be rising. Here we use Brazil’s integrated health systems data to develop a mathematical model, reproducing the complex surveillance systems and providing estimates of HIV incidence, number of people living with HIV (PLHIV), reporting rates and ART initiation rates. An age-structured deterministic model with a flexible spline was used to describe the natural history of HIV along with reporting and treatment rates. Individual-level surveillance data for 1,077,295 cases (HIV/AIDS diagnoses, ART dispensations, CD4 counts and HIV/AIDS-related deaths) were used to calibrate the model using Bayesian inference. The results showed a second wave of infections occurring after 2001 and 56,000 (95% Credible Interval 43,000–71,000) new infections in 2015, 37,000 (95% CrI 28,000–54,000) infections in men and 16,000 (95% CrI 10,000–23,000) in women. The estimated number of PLHIV by end-2015 was 838,000 (95% CrI 675,000–1,083,000), with 80% (95% CrI 62–98%) of those individuals reported to the Ministry of Health. Women were more likely to be diagnosed and reported than men; 86.8% of infected women had been reported compared with 75.7% of men. Likewise, ART initiation rates for women were higher than those for men. The second wave contradicts previous estimates of HIV incidence trends in Brazil and there were persistent differences in the rates of accessing care between men and women. Nevertheless, the Brazilian HIV program has achieved high rates of detection and treatment, making considerable progress over the past ten years. more...

Drosophila suzukii Matsumura is a recent invasive fruit pest in North and South America and Europe, causing pre-harvest damage and significant economic losses to crops. Little is known about biological control of D. suzukii ; here we report the predatory capability of Dalotia (Atheta) coriaria Kraatz, a commercially available control agent against small dipteran pests, and develop molecular tools to assess predation. Da. coriaria showed a Type II functional response to all D. suzukii instars, with maximal consumption of 26 first, 15 second, and 6 third instars per beetle per day. No pupae were consumed. When raspberries with 11–21 larvae (2nd–3rd instar) per berry were exposed to six Da. coriaria for 4.5 d, a 50% reduction in infestation occurred. A primer pair for D. suzukii was designed that produced a 112 bp amplicon from the mtDNA CO1 gene. Of 19 Drosophila species tested, DNA from one species in the invaded range of D. suzukii was amplified, but it was distinguishable from D. suzukii due to different amplicon melting temperatures. A standard curve was created, relating amount of second instar D. suzukii DNA to Cq values (amount of fluorescence) generated by qPCR. In a feeding trial, the half-life of D. suzukii DNA was 2.3 h in Da. coriaria , but the estimated median detection time was 25.9 h. D. suzukii DNA was detected in Da. coriaria exposed to infested raspberries, but DNA quantity in beetles was only weakly related to predation rates. The control potential of Da. coriaria against D. suzukii should be further assessed, and molecular tools used to identify other D. suzukii predators. more...

Glow-worms (larvae of dipteran genus Arachnocampa) are restricted to moist habitats where they capture flying prey using snares composed of highly extensible silk fibres and sticky mucus droplets. Little is known about the composition or structure of glow-worm snares, or the extent of possible convergence between glow-worm and arachnid capture silks. We characterised Arachnocampa richardsae silk and mucus using X-ray scattering, Fourier transform infrared spectroscopy and amino acid analysis. Silk but not mucus contained crystallites of the cross-β-sheet type, which occur in unrelated insect silks but have not been reported previously in fibres used for prey capture. Mucus proteins were rich in Gly (28.5%) and existed in predominantly a random coil structure, typical of many adhesive proteins. In contrast, the silk fibres were unusually rich in charged and polar residues, particularly Lys (18.1%), which we propose is related to their use in a highly hydrated state. Comparison of X-ray scattering, infrared spectroscopy and amino acid analysis data suggests that silk fibres contain a high fraction of disordered protein. We suggest that in the native hydrated state, silk fibres are capable of extension via deformation of both disordered regions and cross-β-sheet crystallites, and that high extensibility is an adaptation promoting successful prey capture. This study illustrates the rich variety of protein motifs that are available for recruitment into biopolymers, and how convergently evolved materials can nevertheless be based on fundamentally different protein structures. more...

Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is a worldwide emerging pest of soft fruits, but its cold tolerance has not been thoroughly explored. We determined the cold tolerance strategy, low temperature thermal limits, and plasticity of cold tolerance in both male and female adult D. suzukii. We reared flies under common conditions (long days, 21°C; control) and induced plasticity by rapid cold-hardening (RCH, 1h at 0°C followed by 1h recovery), cold acclimation (CA, 5 days at 6°C) or acclimation under fluctuating temperatures (FA). D. suzukii had supercooling points (SCPs) between -16 and -23°C, and were chill-susceptible. 80% of control flies were killed after 1h at -7.2°C (males) or -7.5°C (females); CA and FA improved survival of this temperature in both sexes, but RCH did not. 80% of control flies were killed after 70 h (male) or 92 h (female) at 0°C, and FA shifted this to 112 h (males) and 165 h (females). FA flies entered chill coma (CTmin) at approximately -1.7°C, which was ca. 0.5°C colder than control flies; RCH and CA increased the CTmin compared to controls. Control and RCH flies exposed to 0°C for 8h took 30-40 min to recover movement, but this was reduced to10 min in CA and FA. Flies placed outside in a field cage in London, Ontario, were all killed by a transient cold snap in December. We conclude that adult phenotypic plasticity is not sufficient to allow D. suzukii to overwinter in temperate habitats, and suggest that flies could overwinter in association with built structures, or that there may be additional cold tolerance imparted by developmental plasticity. more...

This work reports a model and Monte Carlo simulations of excluded volume mediated interactions between colloids and topographically patterned substrates in the presence of thermosensitive depletants. The model is matched to experiments to yield density, free energy, and potential energy landscapes that quantitatively capture particle microstructures varying from immobilized non-close packed configurations to random fluid states. A numerical model of local excluded volume affects is developed to enable computation of local depletion attraction in the presence of arbitrary geometries. Our findings demonstrate a quantitative modeling method to interpret and predict how surface patterns mediate local depletion interactions, which enables the design of colloidal based materials and devices. more...

During early zebrafish embryogenesis, spontaneous tail contractions represent the first sign of locomotion and result from innervation of primary motoneuron axons to target axial muscles. Based on a high-content screen, we previously demonstrated that exposure of zebrafish embryos to abamectin – an avermectin insecticide – from 5–25 hours post-fertilization (hpf) abolished spontaneous activity in the absence of effects on survival and gross morphology. Therefore, the objective of this study was to begin investigating the mechanism of abamectin-induced hypoactivity in zebrafish. Similar to 384-well plates, static exposure of embryos to abamectin from 5–25 hpf in glass beakers resulted in elimination of activity at low micromolar concentrations. However, abamectin did not affect neurite outgrowth from spinal motoneurons and, compared with exposure from 5–25 hpf, embryos were equally susceptible to abamectin-induced hypoactivity when exposures were initiated at 10 and 23 hpf. Moreover, immersion of abamectin-exposed embryos in clean water resulted in complete recovery of spontaneous activity relative to vehicle controls, suggesting that abamectin reversibly activated ligand-gated chloride channels and inhibited neurotransmission. To test this hypothesis, we pretreated embryos to vehicle or non-toxic concentrations of fipronil or endosulfan – two insecticides that antagonize the γ-aminobutyric acid (GABA) receptor – from 5–23 hpf, and then exposed embryos to vehicle or abamectin from 23–25 hpf. Interestingly, activity levels within abamectin-exposed embryos pretreated with either antagonist were similar to embryos exposed to vehicle alone. Using quantitative PCR and phylogenetic analyses, we then confirmed the presence of GABA receptor α1 and β2 subunits at 5, 10, and 23 hpf, and demonstrated that zebrafish GABA receptor subunits are homologous to mammalian GABA receptor subunits. Overall, our data collectively suggest that abamectin induces rapid and reversible hypoactivity within early zebrafish embryos, an effect that may be mediated through the GABA receptor. more...

Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may interact with human RARs, we then exposed Chinese hamster ovary cells stably transfected with chimeric human RARα-, RARβ-, or RARγ to TPP in the presence of RA, and found that TPP significantly inhibited RA-induced luciferase activity in a concentration-dependent manner. Overall, our findings suggest that zebrafish RARs may be involved in mediating TPP-induced developmental toxicity, a mechanism of action that may have relevance to humans. more...

Invasive species can destabilize ecological communities by becoming novel hosts, prey, predators or competitors for native species. They can have lasting effects on population dynamics when they reduce the fitness of native individuals. The establishment and spread of invasive Halyomorpha halys, in Europe and North America, have presented native natural enemies in the introduced areas with such a challenge. The native parasitoids readily parasitize eggs of H. halys, but their progeny rarely develops in fresh eggs of this host. The barriers to successful development of native parasitoids in H. halys eggs remain unidentified, and the affected developmental processes therein remain unclear. To determine the timing of failed development of native parasitoids in fresh H. halys eggs, we examined the temporal development of the Trissolcus euschisti parasitoid within suitable (Podisus maculiventis) and unsuitable (Halyomorpha halys) host eggs using a DNA barcode-based approach, and in situ 3D visualization by X-ray micro-computed tomography (micro-CT). Trissolcus euschisi parasitoid development in fresh H. halys eggs fails soon after parasitization either during the egg stage or during early-stage larval development, as limited or no larval development was observed 24 h after initial parasitization. In light of these findings, we propose a time window for further investigation of several potential mechanisms that might result in failed parasitoid development in H. halys. more...

Phosphatase and tensin homolog (PTEN)-induced kinase 1 (Pink1) is involved in mitochondrial quality control, which is essential for maintaining energy production and minimizing oxidative damage from dysfunctional/depolarized mitochondria. Pink1 mutations are the second most common cause of autosomal recessive Parkinson’s disease (PD). In addition to characteristic motor impairments, PD patients also commonly exhibit cognitive impairments. As the hippocampus plays a prominent role in cognition, we tested if loss of Pink1 in mice influences learning and memory. While wild-type mice were able to perform a contextual discrimination task, age-matched Pink1 knockout (Pink1(−/−)) mice showed an impaired ability to differentiate between two similar contexts. Similarly, Pink1(−/−) mice performed poorly in a delayed alternation task as compared to age-matched controls. Poor performance in these cognitive tasks was not the result of overt hippocampal pathology. However, a significant reduction in hippocampal tyrosine hydroxylase (TH) protein levels was detected in the Pink1(−/−) mice. This decrease in hippocampal TH levels was also associated with reduced DOPA decarboxylase and dopamine D2 receptor levels, but not post-synaptic dopamine D1 receptor levels. These presynaptic changes appeared to be selective for dopaminergic fibers as hippocampal dopamine beta hydroxylase, choline acetyltransferase, and tryptophan hydroxylase levels were unchanged in Pink1(−/−) mice. Administration of the dopamine D1 receptor agonist SKF38393 to Pink1(−/−) mice was found to improve performance in the context discrimination task. Taken together, our results show that Pink1 loss may alter dopamine signaling in the hippocampus, which could be a contributing mechanism for the observed learning and memory impairments. more...

In this work we investigate the use of coiled-coil silk proteins, produced in recombinant Escherichia coli, as a new material for immobilizing biosensors. Myoglobin was embedded in transparent honeybee silk protein films. Immobilized myoglobin maintained a high affinity for nitric oxide (KD NO=52 µM) and good sensitivity with a limit of detection of 5 µM. The immobilized myoglobin–silk protein film was stable and could be stored as a dry film at room temperature for at least 60 days. The effect of immobilization on the structure of myoglobin was fully investigated using UV/visible, Fourier Transform Infrared and Raman spectroscopy, which indicated a weakening in the strength of the iron–histidine bond. This study demonstrates that recombinant coiled-coil silk proteins provide a safe and environmentally friendly alternative to sol–gels for stabilizing heme proteins for use as optical biosensors. more...

Research finds that adolescents gravely overestimate their risk of death and that these pessimistic attitudes correlate with risky behaviors undermining health and well-being; however, it remains unclear why adolescents have negative expectations about their survival. Because youth are most likely to be exposed to violence (as victims and/or witnesses), perhaps these experiences are key in undermining expectations about the future. We explored the effect of direct and indirect exposures to violence-across various contexts-on adolescents' survival expectations.Using data from the National Longitudinal Study of Adolescent Health, we tested the effect of violent experiences: individual direct and vicarious violence, familial and relational violence, school violence, and community violence on adolescents' expectations of surviving to 35 years of age.Victims of childhood physical abuse were less likely to expect to survive to 35 years of age. Although not significant at the conventional p.05 level, violent victimization (being jumped, cut/stabbed, shot, or threatened with a weapon) and intimate partner violence were marginally associated with decreased survival expectations (p.10). School and community violence undermined expectations at the bivariate level, but became nonsignificant after adjustments for individual demographic characteristics.Violent victimization in childhood and adolescence is a public health issue with both immediate and long-term consequences. Violence exposure severely compromises individuals' optimism about the future and places them at risk for behaviors that can further undermine well-being. Practitioners should be mindful of diminished survival expectations as a less overt consequence of exposure to violence. more...

Silk production is integral to the construction of nests or cocoons for many Aculeata, stinging Hymenopterans such as ants, bees and wasps. Here we report the sequences of new aculeate silk proteins and compare cross-linking among nine native silks from three bee species (Apis mellifera, Bombus terrestris and Megachile rotundata), three ant species (Myrmecia forficata, Oecophylla smaragdina and Harpegnathos saltator) and three hornets (Vespa analis, Vespa simillima and Vespa mandarinia). The well studied silks of spiders and silkworms are comprised of large proteins that are cross-linked and stabilized predominantly by intra and intermolecular beta sheet structure. In contrast, the aculeate silks are comprised of relatively small proteins that contain central coiled coil domains and comparatively reduced amounts of beta sheet structure. The hornet silks, which have the most beta sheet structure and the greatest amount of amino acid sequence outside the coiled-coil domains, dissolve in concentrated LiBr solution and appear to be stabilized predominantly by beta sheet structure like the classic silks. In contrast, the ant and bee silks, which have less beta sheet and less sequence outside the coiled-coil domains, could not be dissolved in LiBr and appear to be predominantly stabilized by covalent cross-linking. The iso-peptide cross-linker, ε-(γ-glutamyl)-lysine that is produced by transglutaminase enzymes, was demonstrated to be present in all silks by mass spectrometry, but at greater levels in silks of ants and bees. The bee silks and ant cocoons, but not the Oecophylla nest silks, appeared to be further stabilized by tanning reactions. more...