The detection of a strong episignature for Chung-Jansen syndrome, partially overlapping with Börjeson-Forssman-Lehmann and White-Kernohan syndromes.

Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It is caused by pathogenic variants in the PHIP gene that encodes for the Pleckstrin homology domain-interacting protein, which is part of an epigenetic modifier protein complex. Therefore, we hypothesized that PHIP haploinsufficiency may impact genome-wide DNA methylation (DNAm). We assessed the DNAm profiles of affected individuals with pathogenic and likely pathogenic PHIP variants with Infinium Methylation EPIC arrays and report a specific and sensitive DNAm episignature biomarker for Chung-Jansen syndrome. In addition, we observed similarities between the methylation profile of Chung-Jansen syndrome and that of functionally related and clinically partially overlapping genetic disorders, White-Kernohan syndrome (caused by variants in DDB1 gene) and Börjeson-Forssman-Lehmann syndrome (caused by variants in PHF6 gene). Based on these observations we also proceeded to develop a common episignature biomarker for these disorders. These newly defined episignatures can be used as part of a multiclass episignature classifier for screening of affected individuals with rare disorders and interpretation of genetic variants of unknown clinical significance, and provide further insights into the common molecular pathophysiology of the clinically-related Chung-Jansen, Börjeson-Forssman-Lehmann and White-Kernohan syndromes.

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.

Deformed wing virus of honey bees is inactivated by cold plasma ionized hydrogen peroxide.

Deformed wing virus (DWV) is a widespread pathogen of Apis mellifera honey bees, and is considered a major causative factor for the collapse of infected honey bee colonies. DWV can be horizontally transmitted among bees through various oral routes, including via food sharing and by interactions of bees with viral-contaminated solid hive substrates. Cold plasma ionized hydrogen peroxide (iHP) is used extensively by the food production, processing and medical industries to clean surfaces of microbial contaminants. In this study, we investigated the use of iHP to inactivate DWV particles in situ on a solid substrate. iHP-treated DWV sources were ~105-fold less infectious when injected into naïve honey bee pupae compared to DWV receiving no iHP treatment, matching injected controls containing no DWV. iHP treatment also greatly reduced the incidence of overt DWV infections (i.e., pupae having >109 copies of DWV). The level of DWV inactivation achieved with iHP treatment was higher than other means of viral inactivation such as gamma irradiation, and iHP treatment is likely simpler and safer. Treatment of DWV contaminated hive substrates with iHP, even with honey bees present, may be an effective way to decrease the impacts of DWV infection on honey bees.

The vectoring competence of the mite Varroa destructor for deformed wing virus of honey bees is dynamic and affects survival of the mite.

The ectoparasitic mite, Varroa destructor and the viruses it vectors, including types A and B of Deformed wing virus (DWV), pose a major threat to honey bees, Apis mellifera. Analysis of 256 mites collected from the same set of field colonies on five occasions from May to October 2021 showed that less than a half of them, 39.8% (95% confidence interval (CI): 34.0 - 46.0%), were able to induce a high (overt) level DWV infection with more than 109 viral genomes per bee in the pupa after 6 days of feeding, with both DWV-A and DWV-B being vectored at similar rates. To investigate the effect of the phoretic (or dispersal) stage on adult bees on the mites' ability to vector DWV, the mites from two collection events were divided into two groups, one of which was tested immediately for their infectiveness, and the other was kept with adult worker bees in cages for 12 days prior to testing their infectiveness. We found that while 39.2% (95% CI: 30.0 - 49.1%) of the immediately tested mites induced overt-level infections, 12-day passage on adult bees significantly increased the infectiousness to 89.8% (95% CI: 79.2 - 95.6%). It is likely that Varroa mites that survive brood interruptions in field colonies are increasingly infectious. The mite lifespan was affected by the DWV type it transmitted to pupae. The mites, which induced high DWV-B but not DWV-A infection had an average lifespan of 15.5 days (95% CI: 11.8 - 19.2 days), which was significantly shorter than those of the mites which induced high DWV-A but not DWV-B infection, with an average lifespan of 24.3 days (95% CI: 20.2 - 28.5), or the mites which did not induce high levels of DWV-A or DWV-B, with an average survival of 21.2 days (95% CI: 19.0 - 23.5 days). The mites which transmitted high levels of both DWV-A and DWV-B had an intermediate average survival of 20.5 days (95% CI: 15.1 - 25.9 days). The negative impact of DWV-B on mite survival could be a consequence of the ability of DWV-B, but not DWV-A to replicate in Varroa.