The efficacy of 1-allyloxy-4-propoxybenzene (3c{3,6}) against Varroa destructor mites in honey bee colonies from Maryland, USA.

Varroa destructor Oud (Acari: Varroidae) is a harmful ectoparasite of Apis mellifera L. honey bees causing widespread colony losses in Europe and North America. To control populations of these mites, beekeepers have an arsenal of different treatments, including both chemical and nonchemical options. However, nonchemical treatments can be labor intensive, and Varroa has gained resistance to some conventional pesticides, and the use of other chemical treatments is restricted temporally (e.g., cannot be applied during periods of honey production). Thus, beekeepers require additional treatment options for controlling mite populations. The compound 1-allyloxy-4-propoxybenzene (3c{3,6}) is a diether previously shown to be a strong feeding deterrent against Lepidopteran larvae and a repellent against mosquitoes and showed promise as a novel acaricide from laboratory and early field trials. Here we test the effect of the compound, applied at 8 g/brood box on wooden release devices, on honey bees and Varroa in field honey bee colonies located in Maryland, USA, and using a thymol-based commercial product as a positive control. 3c{3,6} had minimal effect on honey bee colonies, but more tests are needed to determine whether it affected egg production by queens. Against Varroa3c{3,6} had an estimated efficacy of 78.5%, while the positive control thymol product showed an efficacy of 91.3%. 3c{3,6} is still in the development stage, and the dose or application method needs to be revisited.

Embodied Resilience: A Quasi-Experimental Exploration of the Effects of a Trauma-Informed Yoga and Mindfulness Curriculum in Carceral Settings.

Individuals who are incarcerated likely experience trauma or exacerbate existing trauma, which has significant health risks. Trauma-informed care aims to address the experienced trauma. The current study explored the effect of a trauma-informed yoga and mindfulness curriculum in carceral settings. In this quasi-experimental study, participants (n = 326) were assigned to either six weekly sessions of 60-minute group trauma-informed yoga and mindfulness or a waitlist control condition. Stress and mood were measured pre- and postclass, whereas coping, emotional awareness, emotional regulation, anxiety, anger management, compassion, self-compassion, forgiveness, and posttraumatic growth were measured pre- and postcurriculum. The trauma-informed group showed a significant increase in mood and decrease in stress after participation in class. Participants were more likely to use positive coping skills, experienced greater levels of forgiveness, and were more likely to experience posttraumatic growth after completing programming as compared to a control group. Qualitative data highlighted perceived improvements in mood, physical health, communication with peers, coping with anxiety and anger, focus and self-control, optimism, acceptance, and open-mindedness. The qualitative data also demonstrated the importance of supportive relationships outside of participants' peers (i.e., instructors). Outcomes suggest benefit of a trauma-informed yoga and mindfulness curriculum in aiding people who are incarcerated in supporting mental and physical well-being and building resilience.

Multi-trait genomic prediction improves selection accuracy for enhancing seed mineral concentrations in pea.

Multi-trait genomic selection (MT-GS) has the potential to improve predictive ability by maximizing the use of information across related genotypes and genetically correlated traits. In this study, we extended the use of sparse phenotyping method into the MT-GS framework by split testing of entries to maximize borrowing of information across genotypes and predict missing phenotypes for targeted traits without additional phenotyping expenditure. Using 300 advanced breeding lines from North Dakota State University (NDSU) pulse breeding program and ∼200 USDA accessions that were evaluated for 10 nutritional traits, our results show that the proposed sparse phenotyping aided MT-GS can further improve predictive ability by >12% across traits compared with univariate (UNI) genomic selection. The proposed strategy departed from the previous reports that weak genetic correlation is a limitation to the advantage of MT-GS over UNI genomic selection, which was evident in the partially balanced phenotyping-enabled MT-GS. Our results point to heritability and genetic correlation between traits as possible metrics to optimize and further improve the estimation of model parameters, and ultimately, prediction performance. Overall, our study offers a new approach to optimize the prediction performance using the MT-GS and further highlight strategy to maximize the efficiency of GS in a plant breeding program. The sparse-testing-aided MT-GS proposed in this study can be further extended to multi-environment, multi-trait GS to improve prediction performance and further reduce the cost of phenotyping and time-consuming data collection process.

We extended the use of sparse phenotyping into the multi-trait genomic selection (MT-GS) framework by split testing of entries. The sparse-phenotyping-aided MT-GS can increase predictive ability by >12% across traits. Heritability and genetic correlation are possible metrics to optimize and further improve prediction performance of MT-GS. The sparse-testing-aided MT-GS can be further extended to multi-environment, multi-trait GS framework.

High-Throughput Screening to Identify Small Molecules That Selectively Inhibit APOL1 Protein Level in Podocytes.

High-throughput phenotypic screening is a key driver for the identification of novel chemical matter in drug discovery for challenging targets, especially for those with an unclear mechanism of pathology. For toxic or gain-of-function proteins, small-molecule suppressors are a targeting/therapeutic strategy that has been successfully applied. As with other high-throughput screens, the screening strategy and proper assays are critical for successfully identifying selective suppressors of the target of interest. We executed a small-molecule suppressor screen to identify compounds that specifically reduce apolipoprotein L1 (APOL1) protein levels, a genetically validated target associated with increased risk of chronic kidney disease. To enable this study, we developed homogeneous time-resolved fluorescence (HTRF) assays to measure intracellular APOL1 and apolipoprotein L2 (APOL2) protein levels and miniaturized them to 1536-well format. The APOL1 HTRF assay served as the primary assay, and the APOL2 and a commercially available p53 HTRF assay were applied as counterscreens. Cell viability was also measured with CellTiter-Glo to assess the cytotoxicity of compounds. From a 310,000-compound screening library, we identified 1490 confirmed primary hits with 12 different profiles. One hundred fifty-three hits selectively reduced APOL1 in 786-O, a renal cell adenocarcinoma cell line. Thirty-one of these selective suppressors also reduced APOL1 levels in conditionally immortalized human podocytes. The activity and specificity of seven resynthesized compounds were validated in both 786-O and podocytes.

Discovery of a new class of integrin antibodies for fibrosis.

Lung fibrosis, or the scarring of the lung, is a devastating disease with huge unmet medical need. There are limited treatment options and its prognosis is worse than most types of cancer. We previously discovered that MK-0429 is an equipotent pan-inhibitor of αv integrins that reduces proteinuria and kidney fibrosis in a preclinical model. In the present study, we further demonstrated that MK-0429 significantly inhibits fibrosis progression in a bleomycin-induced lung injury model. In search of newer integrin inhibitors for fibrosis, we characterized monoclonal antibodies discovered using Adimab's yeast display platform. We identified several potent neutralizing integrin antibodies with unique human and mouse cross-reactivity. Among these, Ab-31 blocked the binding of multiple αv integrins to their ligands with IC50s comparable to those of MK-0429. Furthermore, both MK-0429 and Ab-31 suppressed integrin-mediated cell adhesion and latent TGFß activation. In IPF patient lung fibroblasts, TGFß treatment induced profound αSMA expression in phenotypic imaging assays and Ab-31 demonstrated potent in vitro activity at inhibiting αSMA expression, suggesting that the integrin antibody is able to modulate TGFß action though mechanisms beyond the inhibition of latent TGFß activation. Together, our results highlight the potential to develop newer integrin therapeutics for the treatment of fibrotic lung diseases.

Sugar concentration in nectar: a quantitative metric of crop attractiveness for refined pollinator risk assessments.

Those involved with pollinator risk assessment know that agricultural crops vary in attractiveness to bees. Intuitively, this means that exposure to agricultural pesticides is likely greatest for attractive plants and lowest for unattractive plants. While crop attractiveness in the risk assessment process has been qualitatively remarked on by some authorities, absent is direction on how to refine the process with quantitative metrics of attractiveness. At a high level, attractiveness of crops to bees appears to depend on several key variables, including but not limited to: floral, olfactory, visual and tactile cues; seasonal availability; physical and behavioral characteristics of the bee; plant and nectar rewards. Notwithstanding the complexities and interactions among these variables, sugar content in nectar stands out as a suitable quantitative metric by which to refine pollinator risk assessments for attractiveness. Provided herein is a proposed way to use sugar nectar concentration to adjust the exposure parameter (with what is called a crop attractiveness factor) in the calculation of risk quotients in order to derive crop-specific tier I assessments. This Perspective is meant to invite discussion on incorporating such changes in the risk assessment process. © 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Pesticide exposure in honey bees results in increased levels of the gut pathogen Nosema.

Global pollinator declines have been attributed to habitat destruction, pesticide use, and climate change or some combination of these factors, and managed honey bees, Apis mellifera, are part of worldwide pollinator declines. Here we exposed honey bee colonies during three brood generations to sub-lethal doses of a widely used pesticide, imidacloprid, and then subsequently challenged newly emerged bees with the gut parasite, Nosema spp. The pesticide dosages used were below levels demonstrated to cause effects on longevity or foraging in adult honey bees. Nosema infections increased significantly in the bees from pesticide-treated hives when compared to bees from control hives demonstrating an indirect effect of pesticides on pathogen growth in honey bees. We clearly demonstrate an increase in pathogen growth within individual bees reared in colonies exposed to one of the most widely used pesticides worldwide, imidacloprid, at below levels considered harmful to bees. The finding that individual bees with undetectable levels of the target pesticide, after being reared in a sub-lethal pesticide environment within the colony, had higher Nosema is significant. Interactions between pesticides and pathogens could be a major contributor to increased mortality of honey bee colonies, including colony collapse disorder, and other pollinator declines worldwide.