Evaluation of Harpin for the Control of Insect-Vectored Bacterial Wilt of Pumpkin and Testing of PMR-Pumpkin and Squash Varieties for Their Reaction to Beetle Feeding Activity and Bacterial Wilt Inoculations

NYS IPM Type: Project ReportThe goals of this project were 1) to determine if harpin can suppress the transmission of bacterial wilt (BW) vectored by cucumber beetles and 2) to compare cucurbit crops and varieties for their attractiveness to cucumber beetles and susceptibility to bacterial wilt

A genomic approach to inferring kinship reveals limited intergenerational dispersal in the yellow fever mosquito

Understanding past dispersal and breeding events can provide insight into ecology and evolution, and can help inform strategies for conservation and the control of pest species. However, parent-offspring dispersal can be difficult to investigate in rare species and in small pest species such as mosquitoes. Here we develop a methodology for estimating parent-offspring dispersal from the spatial distribution of close kin, using pairwise kinship estimates derived from genome-wide single nucleotide polymorphisms (SNPs). SNPs were scored in 162 Aedes aegypti (yellow fever mosquito) collected from eight close-set, high-rise apartment buildings in an area of Malaysia with high dengue incidence. We used the SNPs to reconstruct kinship groups across three orders of kinship. We transformed the geographical distances between all kin pairs within each kinship category into axial standard deviations of these distances, then decomposed these into components representing past dispersal events. From these components, we isolated the axial standard deviation of parent-offspring dispersal, and estimated neighbourhood area (129 m), median parent-offspring dispersal distance (75 m), and oviposition dispersal radius within a gonotrophic cycle (36 m). We also analysed genetic structure using distance-based redundancy analysis and linear regression, finding isolation by distance both within and between buildings and estimating neighbourhood size at 268 individuals. These findings indicate the scale required to suppress local outbreaks of arboviral disease and to target releases of modified mosquitoes for mosquito and disease control. Our methodology is readily implementable for studies of other species, including pests and species of conservation significance

The Wolbachia strain wAu provides highly efficient virus transmission blocking in Aedes aegypti

Introduced transinfections of the inherited bacteria Wolbachia can inhibit transmission of viruses by Aedes mosquitoes, and in Ae. aegypti are now being deployed for dengue control in a number of countries. Only three Wolbachia strains from the large number that exist in nature have to date been introduced and characterized in this species. Here novel Ae. aegypti transinfections were generated using the wAlbA and wAu strains. In its native Ae. albopictus, wAlbA is maintained at lower density than the co-infecting wAlbB, but following transfer to Ae. aegypti the relative strain density was reversed, illustrating the strain-specific nature of Wolbachia-host co-adaptation in determining density. The wAu strain also reached high densities in Ae. aegypti, and provided highly efficient transmission blocking of dengue and Zika viruses. Both wAu and wAlbA were less susceptible than wMel to density reduction/incomplete maternal transmission resulting from elevated larval rearing temperatures. Although wAu does not induce cytoplasmic incompatibility (CI), it was stably combined with a CI-inducing strain as a superinfection, and this would facilitate its spread into wild populations. Wolbachia wAu provides a very promising new option for arbovirus control, particularly for deployment in hot tropical climates

Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease

OBJECTIVES: To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: In the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib. RESULTS: Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (SE) of decline in FVC (mL/year) over 52 weeks was -74.5 (19.2) in the placebo group and -49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI -28.9, 79.6]). Among 249 patients with data at week 52, mean (SE) changes in FVC at week 52 were -86.4 (21.1) mL in the placebo group and -39.1 (22.2) mL in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (SE) changes in FVC from baseline to week 52 of SENSCIS-ON were -41.5 (24.0) mL in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and -45.1 (19.1) mL in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON. CONCLUSION: Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD. TRIAL REGISTRATION: ClinicalTrials.gov (https://www.clinicaltrials.gov), NCT02597933 and NCT03313180

Advances in Basic and Translational Research as Part of the Center for the Study of Complex Malaria in India.

The Center for the Study of Complex Malaria in India (CSCMi) is one of 10 International Centers of Excellence in Malaria Research funded by the National Institutes of Health since 2010. The Center combines innovative research with capacity building and technology transfer to undertake studies with clinical and translational impact that will move malaria control in India toward the ultimate goal of malaria elimination/eradication. A key element of each research site in the four states of India (Tamil Nadu, Gujarat, Odisha, and Meghalaya) has been undertaking community- and clinic-based epidemiology projects to characterize the burden of malaria in the region. Demographic and clinical data and samples collected during these studies have been used in downstream projects on, for example, the widespread use of mosquito repellants, the population genomics of Plasmodium vivax, and the serological responses to P. vivax and Plasmodium falciparum antigens that reflect past or present exposure. A focus has been studying the pathogenesis of severe malaria caused by P. falciparum through magnetic resonance imaging of cerebral malaria patients. Here we provide a snapshot of some of the basic and applied research the CSCMi has undertaken over the past 12 years and indicate the further research and/or clinical and translational impact these studies have had

Local Electrical Dyssynchrony during Atrial Fibrillation: Theoretical Considerations and Initial Catheter Ablation Results

Copyright: © 2016 Kuklik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Electrogram-based identification of the regions maintaining persistent Atrial Fibrillation (AF) is a subject of ongoing debate. Here, we explore the concept of local electrical dyssynchrony to identify AF drivers. Methods and Results Local electrical dyssynchrony was calculated using mean phase coherence. High-density epicardial mapping along with mathematical model were used to explore the link between local dyssynchrony and properties of wave conduction. High-density mapping showed a positive correlation between the dyssynchrony and number of fibrillatory waves (R2 = 0.68, p<0.001). In the mathematical model, virtual ablation at high dyssynchrony regions resulted in conduction regularization. The clinical study consisted of eighteen patients undergoing catheter ablation of persistent AF. High-density maps of left atrial (LA) were constructed using a circular mapping catheter. After pulmonary vein isolation, regions with the top 10% of the highest dyssynchrony in LA were targeted during ablation and followed with ablation of complex atrial electrograms. Catheter ablation resulted in termination during ablation at high dyssynchrony regions in 7 (41%) patients. In another 4 (24%) patients, transient organization was observed. In 6 (35%) there was no clear effect. Long-term follow-up showed 65% AF freedom at 1 year and 22% at 2 years. Conclusions Local electrical dyssynchrony provides a reasonable estimator of regional AF complexity defined as the number of fibrillatory waves. Additionally, it points to regions of dynamical instability related with action potential alternans. However, despite those characteristics, its utility in guiding catheter ablation of AF is limited suggesting other factors are responsible for AF persistence

Adhesive and conformational behaviour of mycolic acid monolayers

We have studied the pH-dependent interaction between mycolic acid (MA) monolayers and hydrophobic and hydrophilic surfaces using molecular (colloidal probe) force spectroscopy. In both cases, hydrophobic and hydrophilic monolayers (prepared by Langmuir-Blodgett and Langmuir-Schaefer deposition on silicon or hydrophobized silicon substrates, respectively) were studied. The force spectroscopy data, fitted with classical DLVO (Derjaguin, Landau, Verwey, and Overbeek) theory to examine the contribution of electrostatic and van der Waals forces, revealed that electrostatic forces are the dominant contribution to the repulsive force between the approaching colloidal probe and MA monolayers. The good agreement between data and the DLVO model suggest that beyond a few nm away from the surface, hydrophobic, hydration, and specific chemical bonding are unlikely to contribute to any significant extent to the interaction energy between the probe and the surface. The pH-dependent conformation of MA molecules in the monolayer at the solid-liquid interface was studied by ellipsometry, neutron reflectometry, and with a quartz crystal microbalance. Monolayers prepared by the Langmuir-Blodgett method demonstrated a distinct pH-responsive behaviour, while monolayers prepared by the Langmuir-Schaefer method were less sensitive to pH variation. It was found that the attachment of water molecules plays a vital role in determining the conformation of the MA monolayers. (C) 2010 Elsevier B.V. All rights reserved

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

Wolbachia strain wAlbB maintains high density and dengue inhibition following introduction into a field population of Aedes aegypti

Aedes aegypti mosquitoes carrying the wAlbB Wolbachia strain show a reduced capacity to transmit dengue virus. wAlbB has been introduced into wild Ae. aegypti populations in several field sites in Kuala Lumpur, Malaysia, where it has persisted at high frequency for more than 2 years and significantly reduced dengue incidence. Although these encouraging results indicate that wAlbB releases can be an effective dengue control strategy, the long-term success depends on wAlbB maintaining high population frequencies and virus transmission inhibition, and both could be compromised by Wolbachia–host coevolution in the field. Here, wAlbB-carrying Ae. aegypti collected from the field 20 months after the cessation of releases showed no reduction in Wolbachia density or tissue distribution changes compared to a wAlbB laboratory colony. The wAlbB strain continued to induce complete unidirectional cytoplasmic incompatibility, showed perfect maternal transmission under laboratory conditions, and retained its capacity to inhibit dengue. Additionally, a field-collected wAlbB line was challenged with Malaysian dengue patient blood, and showed significant blocking of virus dissemination to the salivary glands. These results indicate that wAlbB continues to inhibit currently circulating strains of dengue in field populations of Ae. aegypti, and provides additional support for the continued scale-up of Wolbachia wAlbB releases for dengue control