Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/myokymia can result from mutations in this gene.

No abstract

Fungi can play critical roles in host microbiomes (5–7), yet bacterial-fungal interactions are understudied. For insects, fungi are the leading cause of disease (5, 8).

Fungi are the leading cause of insect disease, contributing to the decline of wild and 25 managed populations 1,2 . For ecologically and economically critical species, such as the 26 European honey bee (Apis mellifera), the presence and prevalence of fungal pathogens can 27 have far reaching consequences, endangering other species and threatening food 28 security 3,4,5 . Our ability to address fungal epidemics and opportunistic infections is 29 currently hampered by the limited number of antifungal therapies 6,7 . Novel antifungal 30 treatments are frequently of bacterial origin and produced by defensive symbionts 31 (bacteria that associate with an animal/plant host and protect against natural enemies 89 . 32 Here we examined the capacity of a honey bee-associated bacterium, Bombella apis, to 33 suppress the growth of fungal pathogens and ultimately protect bee brood (larvae and 34 pupae) from infection. Our results showed that strains of B. apis inhibit the growth of two 35 insect fungal pathogens, Beauveria bassiana and Aspergillus flavus, in vitro. This phenotype 36 was recapitulated in vivo; bee brood supplemented with B. apis were significantly less likely 37 to be infected by A. flavus. Additionally, the presence of B. apis reduced sporulation of A. 38 flavus in the few bees that were infected. Analyses of biosynthetic gene clusters across B. 39 apis strains suggest antifungal production via a Type I polyketide synthase. Secreted 40 metabolites from B. apis alone were sufficient to suppress fungal growth, supporting this 41 hypothesis. Together, these data suggest that B. apis protects bee brood from fungal 42 infection by the secretion of an antifungal metabolite. On the basis of this discovery, new 43 antifungal treatments could be developed to mitigate honey bee colony losses, and, in the 44 future, could address fungal epidemics in other species. 45 Emerging fungal pathogens pose major threats to animal and plant populations 2 . Among 46 insects, fungal pathogens are currently the most common causal agents of disease, and 47 historically have plagued insect hosts for over 300 million years 1,10 . In recent years, fungal 48 pathogens have contributed to the unprecedented population decline of honey bees, causing 49 opportunistic infections in already stressed colonies 3,4 . Within the colony, the most susceptible 50individuals are arguably the bee brood (larvae and pupae), which are exposed to fungal 51 pathogens, notably chalkbrood (Ascophaera apis) and stonebrood (Aspergillus flavus) 11,12 . 52 Although the spread of fungal disease among the brood can be limited by the hygienic behavior 53 of honey bee nurses 13 , this behavior does not prevent infection. However, brood fungal infections 54 in other insects are sometimes inhibited by the presence of bacterial symbionts 14,15,8 . Given that 55 honey bee brood are reared in the presence of a handful of bacterial taxa 16,17 , it is possible these 56 microbes play similar defensive roles. Indeed, worker honey bee pathogen susceptibility 57 correlate...

Recent declines in the health of the honey bee have startled researchers and lay people alike as honey bees are agriculture’s most important pollinator. Honey bees are important pollinators of many major crops and add billions of dollars annually to the US economy through their services. One factor that may influence colony health is the microbial community. Indeed, the honey bee worker digestive tract harbors a characteristic community of bee-specific microbes, and the composition of this community is known to impact honey bee health. However, the honey bee is a superorganism, a colony of eusocial insects with overlapping generations where nestmates cooperate, building a hive, gathering and storing food, and raising brood. In contrast to what is known regarding the honey bee worker gut microbiome, less is known of the microbes associated with developing brood, with food stores, and with the rest of the built hive environment. More recently, the microbe Bombella apis was identified as associated with nectar, with developing larvae, and with honey bee queens. This bacterium is related to flower-associated microbes such as Saccharibacter floricola and other species in the genus Saccharibacter, and initial phylogenetic analyses placed it as sister to these environmental bacteria. Here, we used comparative genomics of multiple honey bee-associated strains and the nectar-associated Saccharibacter to identify genomic changes that may be associated with the ecological transition to honey bee association. We identified several genomic differences in the honey bee-associated strains, including a complete CRISPR/Cas system. Many of the changes we note here are predicted to confer upon Bombella the ability to survive in royal jelly and defend themselves against mobile elements, including phages. Our results are a first step towards identifying potential function of this microbe in the honey bee superorganism.