Characterization and Identification of Methods for Phenotyping Soybean Populations With Tolerance to the Soybean Aphid (Hemiptera: Aphididae).

The development of soybeans tolerant to the soybean aphid [Aphis glycines Matsumura (Hemiptera: Aphididae)] remains unexplored. The objectives of this research were to determine the susceptibility of two high-yielding soybean [Glycine max (L.) Merrill (Fabales: Fabaceae)] genotypes involved in a breeding platform to develop aphid-tolerant recombinant inbred lines (RILs); characterize the peroxidase activity and relative expression of peroxidase transcripts in the parents of RILs; and identify an assay to phenotype aphid-tolerant RILs. Enzyme kinetic assays documented the total peroxidase activity for tolerant (KS4202), susceptible (SD76R), and two high-yielding (U09-105007 and U11-611112) soybeans during two vegetative stages (V1 and V3) at three sampling days (D4, D6, and D8 after aphid introduction). Enzyme kinetic assays showed that V3 infested tolerant and U11-611112 plants had significantly higher peroxidase activity than their respective control plants at D4, and infested tolerant plants were also higher than control plants at D6. There were no apparent trends when comparing the expression of peroxidase-specific transcripts in the absence of aphids (basal levels) in both V1 and V3. Relative expression analyses of two peroxidase transcripts (PRX52 and PRX2) performed to compare differences among the soybean genotypes indicated that, despite basal levels being similar for the treatments analyzed, tolerant soybeans had a tendency for a higher expression of PRX52 in the presence of aphids. Based on the different patterns observed and the feasibility of analyses performed in this study, enzyme kinetics using V3 infested plants may be a marker for screening RILs in a breeding program targeting the development of aphid-tolerant soybeans.

Documenting Resistance and Physiological Changes in Soybean Challenged by Aphis glycines Matsumura (Hemiptera: Aphididae).

The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is a limiting factor in soybean production in the North Central region of the USA. The objectives of this work were to identify sources of resistance to A. glycines in 14 soybean genotypes, and also document changes in total protein, peroxidase, and chlorophyll in response to aphid feeding. A reduced number of A. glycines was observed on the genotypes UX 2569-159-2-01 and UX 2570-171- 04, indicating the presence of antixenosis and/or antibiosis. UX 2569-159-2-01 expressed the highest level of resistance; whereas, UX 2570-171-04 had moderate levels of resistance to A. glycines. Chlorophyll content was relatively unaffected by A. glycines, except for a reduction in UX 2569-159-2-01 infested plants at 5 and 15 days after infestation (DAI). No changes were detected in total protein content between infested and control plants for the genotypes analyzed; however, peroxidase activity was higher in infested UX 2570-171-04 at both 5 and 10 DAI. This improvement in peroxidase content in infested UX 2570-171-04 may be playing multiple roles in the plant tolerance.

Gamma spectrometry in the ITWG CMX-4 exercise.

Low enriched uranium samples of unknown origin were analyzed by 16 laboratories in the context of a Collaborative Materials Exercise (CMX), organized by the Nuclear Forensics International Technical Working Group (ITWG). The purpose was to compare and prioritize nuclear forensic methods and techniques, and to evaluate attribution capabilities among participants. This paper gives a snapshot of the gamma spectrometric capabilities of the participating laboratories and summarizes the results achieved by gamma spectrometry.

The impact of treatment for head and neck cancer on positive psychological change within a year of completing treatment.

Head and neck cancer carries a high level of morbidity and mortality. So why could anyone find having such a disease a positive event? The adversity hypothesis of "what doesn't kill you makes you stronger" suggests that people can use adversity to develop as human beings. This positive psychological change has received little attention in relation to head and neck cancer. Responses to the Silver Lining Questionnaire, University of Washington Quality of Life Questionnaire, and Short-Form 12 were collected from a postal survey, 3 to 12 months after the completion of treatment for head and neck cancer. Fifty-two (63%) people returned the survey and were included in the analysis. Time since completion of therapy did not show any relationship with positive psychological change. Tumour stage and treatment regimen both had a relationship with positive change. Participants with lower stage tumours had higher levels of positive change than those with tumours of higher stages. Participants who had surgery alone reported more positive change than those who had surgery with radiotherapy. A social factor related to greater change was being married or living with a partner when compared to living alone. Further research would aid the identification of bio-psychosocial factors that influence the development of positive psychological change and inform the development of rehabilitation interventions.

A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.

Background: Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation has been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention. We performed a randomized phase II study in vascular endothelial growth factor (VEGF) therapy refractory patients to determine whether MK-2206, an allosteric inhibitor of AKT, was more efficacious than the mammalian target of rapamycin inhibitor everolimus. Patients and methods: A total of 43 patients were randomized in a 2:1 distribution, with 29 patients assigned to the MK-2206 arm and 14 to the everolimus arm. Progression-free survival (PFS) was the primary endpoint. Results: The trial was closed at the first futility analysis with an observed PFS of 3.68 months in the MK-2206 arm and 5.98 months in the everolimus arm. Dichotomous response rate profiles were seen in the MK-2206 arm with one complete response and three partial responses in the MK-2206 arm versus none in the everolimus arm. On the other hand, progressive disease was best response in 44.8% of MK2206 versus 14.3% of everolimus-treated patients. MK-2206 induced significantly more rash and pruritis than everolimus, and dose reduction occurred in 37.9% of MK-2206 versus 21.4% of everolimus-treated patients. Genomic analysis revealed that 57.1% of the patients in the PD group had either deleterious TP53 mutations or ATM mutations or deletions. In contrast, none of the patients in the non-PD group had TP53 or ATM defects. No predictive marker for response was observed in this small dataset. Conclusions: Dichotomous outcomes are observed when VEGF therapy refractory patients are treated with MK-2206, and MK-2206 does not demonstrate superiority to everolimus. Additionally, mutations in DNA repair genes are associated with early disease progression, indicating that dysregulation of DNA repair is associated with a more aggressive tumor phenotype in RCC.

How to assess appearance distress and motivation in plastic surgery candidates: Italian validation of Derriford Appearance Scale 59 (DAS 59).

OBJECTIVE: The Derriford Appearance Scale (DAS) 59 was specifically designed to measure psychosocial adjustment in patients with appearance problems. Previous studies using the DAS59 have proven it to be a reliable method of assessing the appearance-related quality of life after plastic surgery procedures. The aim of this study was to develop a valid and reliable Italian version of the DAS59. PATIENTS AND METHODS: The first Italian translation of this questionnaire was conducted according to the DAS59 protocol that was designed by the original authors of the questionnaire. Eight hundred patients participated in this study and filled out three questionnaires (DAS59, General Health Questionnaire (GHQ)12 and Beck's Depression Inventory (BDI)-II). There were 400 adult patients with a history of previous plastic surgeries and 400 adult patients without any personal history of previous plastic surgery procedures. A total of 50 patients were selected randomly for test-retest analysis. RESULTS: The overall internal consistency was excellent (α = 0.95) and equal to that of the original article that first described the scale. There was a good correlation between all the items. Domains demonstrated good internal consistency (Cronbach's alpha) and correlation within themselves. The construct validity of the Italian DAS59 was assessed under convergent validity that confirmed the correlation with scales related to other psychological conditions. GHQ12 showed relevant correlation with DAS59, while BDI-II did not. CONCLUSIONS: A valid and reliable Italian DAS59 version was developed that can be used for research and clinical assessment of patients with appearance problems and concerns, especially before and after plastic surgery procedures.

A review of fundamental principles for animal models of DOHaD research: an Australian perspective.

Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.

Functional proteomics identifies miRNAs to target a p27/Myc/phospho-Rb signature in breast and ovarian cancer.

The myc oncogene is overexpressed in almost half of all breast and ovarian cancers, but attempts at therapeutic interventions against myc have proven to be challenging. Myc regulates multiple biological processes, including the cell cycle, and as such is associated with cell proliferation and tumor progression. We identified a protein signature of high myc, low p27 and high phospho-Rb significantly correlated with poor patient survival in breast and ovarian cancers. Screening of a miRNA library by functional proteomics in multiple cell lines and integration of data from patient tumors revealed a panel of five microRNAs (miRNAs) (miR-124, miR-365, miR-34b*, miR-18a and miR-506) as potential tumor suppressors capable of reversing the p27/myc/phospho-Rb protein signature. Mechanistic studies revealed an RNA-activation function of miR-124 resulting in direct induction of p27 protein levels by binding to and inducing transcription on the p27 promoter region leading to a subsequent G1 arrest. Additionally, in vivo studies utilizing a xenograft model demonstrated that nanoparticle-mediated delivery of miR-124 could reduce tumor growth and sensitize cells to etoposide, suggesting a clinical application of miRNAs as therapeutics to target the functional effect of myc on tumor growth.

The effect of oxygen content during an initial sustained inflation on heart rate in asphyxiated near-term lambs.

OBJECTIVE: At birth, an initial sustained inflation (SI) uniformly aerates the lungs, increases arterial oxygenation and rapidly improves circulatory recovery in asphyxiated newborns. We hypothesised that lung aeration, in the absence of an increase in arterial oxygenation, can increase heart rate (HR) in asphyxiated near-term lambs. INTERVENTIONS: Lambs were delivered and instrumented at 139±2 days of gestation. Asphyxia was induced by umbilical cord clamping and then delaying the onset of ventilation until mean carotid arterial pressures (CAPs) had decreased <20 mm Hg. Lambs then received a single 30-s SI using nitrogen (N2; n=6), 5% oxygen (O2; n=6), 21% O2 (n=6) or 100% O2 (n=6) followed by ventilation in air for 30 min. MAIN OUTCOME MEASURES: HR, CAP and pulmonary blood flow (PBF) were continuously recorded. RESULTS: HR and PBF increased more quickly in lambs resuscitated with 100% and 21% O2 than with 5% O2 or N2. HR and PBF recovery in the 5% O2 group was delayed relative to all other oxygen SI groups. HR in 5%, 21% and 100% O2 groups reached 100 bpm before the SI was complete. HR and PBF in the N2 group did not increase until 10 s after the SI was completed and ventilation was initiated with air. CAP tended to increase quicker in all O2 groups than in N2 group. CONCLUSIONS: Oxygen content during an SI is important for circulatory recovery in asphyxiated lambs. This increase in HR is likely driven by the increase in PBF and venous return to the heart.

Self-inflating bags versus T-piece resuscitator to deliver sustained inflations in a preterm lamb model.

OBJECTIVE: In neonatal resuscitation, the use of a sustained inflation (SI) may facilitate lung aeration. Previous studies comparing different resuscitation devices have shown that one model of self-inflating bag (SIB) could not deliver an SI. We aimed to compare the delivery of an SI using four SIBs with that of a T-piece. STUDY DESIGN: In intubated preterm lambs, we compared four models of SIB fitted with a positive end expiratory pressure (PEEP) valve to a T-piece using a gas flow of 8 L/min. Four operators aimed to deliver three SIs of 20 cm H2O for 30 s. The study was repeated with the PEEP valve removed and again with no flow. We measured duration of SI, average inflation pressure (IP) and analysed the shape of the pressure curves. RESULTS: 204 combinations were analysed. Mean (SD) duration of SI was Ambu 6(2)s, Laerdal 14(8)s, Parker Healthcare 5(1)s, Mayo Healthcare 33(2)s and T-piece 33(1)s. Mean (SD) average IP was Ambu 17(3)cm H2O, Laerdal 17(3)cm H2O, Parker Healthcare 12(5)cm H2O, Mayo Healthcare 21(2)cm H2O and T-piece 20(0)cm H2O. Duration of SI and average IP was significantly different between SIBs (all p<0.001). The findings were substantially unchanged when PEEP valve and flow were removed (all p>0.05). Only the Mayo system delivered SIs with duration and average IP not significantly different from the T-piece (p>0.05). CONCLUSIONS: The performance of the four SIBs tested varied considerably. Some are able to deliver an SI even in the absence of gas flow. This may be useful in a resource-limited setting with no gas supply.

Characterization of Peroxidase Changes in Tolerant and Susceptible Soybeans Challenged by Soybean Aphid (Hemiptera: Aphididae).

Changes in protein content, peroxidase activity, and isozyme profiles in response to soybean aphid feeding were documented at V1 (fully developed leaves at unifoliate node, first trifoliate leaf unrolled) and V3 (fully developed leaf at second trifoliate node, third trifoliate leaf unrolled) stages of soybean aphid-tolerant (KS4202) and -susceptible (SD76R) soybeans. Protein content was similar between infested and control V1 and V3 stage plants for both KS4202 and SD76R at 6, 16, and 22 d after aphid introduction. Enzyme kinetics studies documented that control and aphid-infested KS4202 V1 stage and SD76R V1 and V3 stages had similar levels of peroxidase activity at the three time points evaluated. In contrast, KS4202 aphid-infested plants at the V3 stage had significantly higher peroxidase activity levels than control plants at 6 and 22 d after aphid introduction. The differences in peroxidase activity observed between infested and control V3 stage KS4202 plants at these two time points suggest that peroxidases may be playing multiple roles in the tolerant plant. Native gels stained for peroxidase were able to detect differences in the isozyme profiles of aphid-infested and control plants for both KS4202 and SD76R.

Evaluation of late vegetative and reproductive stage soybeans for resistance to soybean aphid (Hemiptera: Aphididae).

The soybean aphid, Aphis glycines Matsumura, has become the most significant soybean [Glycine max (L.) Merrill] insect pest in the north central soybean production region of North America. The objectives of this research were to measure selected genotypes for resistance to the soybean aphid in the later vegetative and reproductive stages under field conditions, and confirm the presence of tolerance in KS4202. The results from 2007 to 2011 indicate that KS4202 can support aphid populations with minimal yield loss at levels where significant yield loss would be expected in most other genotypes. The common Nebraska cultivar, 'Asgrow 2703', appears to show signs of tolerance as well. None of the yield parameters were significantly different between the aphid infested and noninfested treatments. Based on our results, genotypes may compensate for aphid feeding in different ways. Asgrow 2703 appears to produce a similar number of seeds as its noninfested counterpart, although the seeds produced are slightly smaller. Field evaluation of tolerance in KS4202 indicated a yield loss of only 13% at 34,585-53,508 cumulative aphid-days, when 24-36% yield loss would have been expected.

Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep.

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40-42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

The impact of maternal synthetic glucocorticoid administration in late pregnancy on fetal and early neonatal hypothalamic-pituitary-adrenal axes regulatory genes is dependent upon dose and gestational age at exposure.

In this study, we determined the gene and/or protein expression of hypothalamic-pituitary-adrenal (HPA) axis regulatory molecules following synthetic glucocorticoid exposures. Pregnant sheep received intramuscular saline or betamethasone (BET) injections at 104 (BET-1), 104 and 111(BET-2) or 104, 111 and 118 (BET-3) days of gestation (dG). Samples were collected at numerous time-points between 75 dG and 12 weeks postnatal age. In the BET-3 treatment group, fetal plasma cortisol levels were lower at 145 dG than controls and gestational length was lengthened significantly. The cortisol:adrenocorticotropic hormone (ACTH) ratio in fetal plasma of control and BET-3 fetuses rose significantly between132 and 145 dG, and remained elevated in lambs at 6 and 12 weeks of age; this rise was truncated at day 145 in fetuses of BET-3 treated mothers. After BET treatment, fetal and postnatal pituitary proopiomelanocortin mRNA levels were reduced from 109 dG to 12 weeks postnatal age; pituitary prohormone convertase 1 and 2 mRNA levels were reduced at 145 dG and postnatally; hypothalamic arginine vasopressin mRNA levels were lowered at all time-points, but corticotrophin-releasing hormone mRNA levels were reduced only in postnatal lambs. Maternal BET increased late fetal and/or postnatal adrenal mRNA levels of ACTH receptor and 3ß hydroxysteroid dehydrogenase but decreased steroidogenic acute regulatory protein and P450 17-α hydroxylase. The altered mRNA levels of key HPA axis regulatory proteins after maternal BET injections suggests processes that may subserve long-term changes in HPA activity in later life after prenatal exposure to synthetic glucocorticoids.

Effects of thiamethoxam seed treatments on soybean aphid (Hemiptera: Aphididae) feeding behavior.

Since its discovery in North America in 2000, the soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), has rapidly become an important pest of soybean [Glycine max (L.) Merrill], sometimes resulting in significant yield losses. Previous research has documented the toxicity of neonicotinoid seed treatments to soybean aphids, but control under field conditions has been inconsistent. Imidacloprid, a popular neonicotinoid insecticide, has been shown to exhibit antifeedant effects on aphids. Antifeedant activity has not been demonstrated for other neonicotinoids, including thiamethoxam. This research investigated the effects of a thiamethoxam seed treatment on soybean aphid feeding behavior by using electronic penetration graphs (EPG) to visualize stylet penetration behavior. Soybean aphid feeding behavior was assessed for 9 h on thiamethoxam-treated and untreated soybeans (V2 and V4 stages). Because results were inconclusive from initial experiments, a study was conducted to document the effects of thiamethoxam-treated soybeans on soybean aphid survival. The seed treatment was shown to negatively affect aphid survival at 4, 8, and 11 d after aphid introduction. A subsequent EPG study then was designed to document soybean aphid feeding behavior for 15 h, after an initial exposure of 9 h to thiamethoxam-treated soybeans. In this study, the exposed aphids exhibited significant differences in feeding behavior compared with those aphids feeding on untreated soybeans. Soybean aphids on thiamethoxam-treated soybeans spent significantly less time feeding in the sieve element phase, with a greater duration of nonprobing events. These studies suggest soybean aphids are unable to ingest phloem sap, which may be another important element in seed treatment protection.

Evaluation of the effectiveness of Face IT, a computer-based psychosocial intervention for disfigurement-related distress.

Some people who have a visible difference (disfigurement) experience psychosocial adjustment problems that can lead to social anxiety and isolation. The aim of this study was to assess the effectiveness of a new computerised CBT-based intervention (Face IT) in reducing anxiety and appearance-related distress for individuals with visible differences. Face IT was tested against a non-intervention control group and standard CBT-based face-to-face delivery. Eighty-three participants were assessed at four time points using the Hospital Anxiety and Depression Scales, Derriford Appearance Scale-24, Body Image Quality of Life Inventory and Fear of Negative Evaluation (FNE). The findings indicate a significant reduction in anxiety and appearance-related distress in both the Face IT intervention and the face-to-face condition. Similar findings were reported for depressive symptoms and FNE. Results at the three and six months follow-up demonstrate increased improvements in psychological functioning with both interventions. This new online psychosocial intervention has been found to be effective at reducing anxiety, depression and appearance concerns amongst individuals with disfigurements, whilst increasing positive adjustment. A remote-access, computer-based intervention offers the potential to provide psychosocial support more easily and in a cost-effective manner to adults with appearance-related distress.

The cerebral critical oxygen threshold of ventilated preterm lambs and the influence of antenatal inflammation.

Perinatal inflammation is associated with adverse neurodevelopmental outcomes, which may be partly due to changes in the cerebral oxygen delivery/consumption relationship. We aimed to determine the critical oxygen delivery threshold of the brain of preterm, ventilated lambs and to determine whether the critical threshold is affected by exposure to inflammation in utero. Pregnant ewes received intra-amniotic injection of lipopolysaccharide or saline at 125 or 127 days of gestation. Pulmonary and systemic flow probes and catheters were surgically positioned in the fetus immediately before delivery at 129 days of gestation. After delivery, lambs were ventilated for 90 min using a positive end-expiratory pressure recruitment strategy. Cardio-respiratory variables and blood gases were measured regularly. Systemic and cerebral oxygen delivery, consumption (Fick), and extraction were calculated, and the relationship between cerebral delivery and consumption analyzed. Linear regression was used to define the transition or "critical" oxygen threshold as the point at which the slope of the oxygen delivery/consumption curve changed to be > 10°. Four subgroups were defined according to the calculated critical threshold. A total of 150 measurements were recorded in 18 lambs. Fetal cerebral oxygen consumption was increased by antenatal lipopolysaccharide (P < 0.05). The postnatal critical oxygen threshold was 3.6 ml·kg⁻¹·min⁻¹, corresponding to cerebral oxygen consumption of 0.73 ml·kg⁻¹·min⁻¹. High oxygen delivery and consumption were associated with increased pulmonary and carotid blood flow and systemic extraction compared with low oxygen delivery and consumption. No postnatal effect of antenatal inflammation was observed. Inflammation in utero increases fetal, but not postnatal, cerebral oxygen consumption. Adverse alterations to pulmonary blood flow can result in reduced cerebral blood flow, oxygen delivery, and consumption. Regardless of exposure to inflammation, there is a consistent postnatal relationship between cerebral oxygen delivery and consumption.

Dose-response relationships of clothianidin, imidacloprid, and thiamethoxam to Blissus occiduus (Hemiptera: Blissidae).

The western chinch bug, Blissus occiduus Barber (Hemiptera: Blissidae), has emerged as a serious pest of buffalograss, Buchlod dactyloides (Nuttall) Engelmann. In general, neonicotinoid insecticides effectively control a variety of turfgrass insects, particularly phloem-feeding pests. However, because of well documented inconsistencies in control, these compounds are generally not recommended for chinch bugs. This study was designed to document the contact and systemic toxicity of three neonicotinoid insecticides (clothianidin, imidacloprid, and thiamethoxam) to B. occiduus. In contact bioassays, thiamethoxam was approximately 20-fold less toxic than clothianidin or imidacloprid to B. occiduus nymphs and three-fold more toxic to adults. In adult systemic bioassays, thiamethoxam was up to five-fold more toxic than clothianidin or imidacloprid. Interestingly, thiamethoxam was significantly more toxic to adults than to nymphs in both contact and systemic bioassays. This was not observed with clothianidin or imidacloprid. Bifenthrin, used for comparative purposes, exhibited 1844-fold and 122-fold increase in toxicity to nymphs and adults, respectively. These results provide the first documentation of the relative toxicity of these neonicotinoid insecticides to B. occiduus.