Functional and Pathological Effects of α-Synuclein on Synaptic SNARE Complexes.

α-Synuclein is an abundant protein at the neuronal synapse that has been implicated in Parkinson's disease for over 25 years and characterizes the hallmark pathology of a group of neurodegenerative diseases now known as the synucleinopathies. Physiologically, α-synuclein exists in an equilibrium between a synaptic vesicle membrane-bound α-helical multimer and a cytosolic largely unstructured monomer. Through its membrane-bound state, α-synuclein functions in neurotransmitter release by modulating several steps in the synaptic vesicle cycle, including synaptic vesicle clustering and docking, SNARE complex assembly, and homeostasis of synaptic vesicle pools. These functions have been ascribed to α-synuclein's interactions with the synaptic vesicle SNARE protein VAMP2/synaptobrevin-2, the synaptic vesicle-attached synapsins, and the synaptic vesicle membrane itself. How α-synuclein affects these processes, and whether disease is due to loss-of-function or gain-of-toxic-function of α-synuclein remains unclear. In this review, we provide an in-depth summary of the existing literature, discuss possible reasons for the discrepancies in the field, and propose a working model that reconciles the findings in the literature.

17q12 deletion syndrome mouse model shows defects in craniofacial, brain and kidney development, and glucose homeostasis.

17q12 deletion (17q12Del) syndrome is a copy number variant (CNV) disorder associated with neurodevelopmental disorders and renal cysts and diabetes syndrome (RCAD). Using CRISPR/Cas9 genome editing, we generated a mouse model of 17q12Del syndrome on both inbred (C57BL/6N) and outbred (CD-1) genetic backgrounds. On C57BL/6N, the 17q12Del mice had severe head development defects, potentially mediated by haploinsufficiency of Lhx1, a gene within the interval that controls head development. Phenotypes included brain malformations, particularly disruption of the telencephalon and craniofacial defects. On the CD-1 background, the 17q12Del mice survived to adulthood and showed milder craniofacial and brain abnormalities. We report postnatal brain defects using automated magnetic resonance imaging-based morphometry. In addition, we demonstrate renal and blood glucose abnormalities relevant to RCAD. On both genetic backgrounds, we found sex-specific presentations, with male 17q12Del mice exhibiting higher penetrance and more severe phenotypes. Results from these experiments pinpoint specific developmental defects and pathways that guide clinical studies and a mechanistic understanding of the human 17q12Del syndrome. This mouse mutant represents the first and only experimental model to date for the 17q12 CNV disorder. This article has an associated First Person interview with the first author of the paper.

Acute exposure to low-dose radiation disrupts reproduction and shortens survival of Wasmannia auropunctata (Hymenoptera: Formicidae) queens.

Irradiation is a postharvest quarantine treatment option to control ants and other hitchhiker pests on fresh horticultural products exported from Hawaii. The radiotolerance of the invasive little fire ant, Wasmannia auropunctata (Roger) (Hymenoptera: Formicidae: Myrmicinae), was studied to determine a dose sufficient for its control. Queens from each of five laboratory microcolonies started from five geographic locations in Argentina were irradiated at 20, 50, 70, or 100 Gy or left untreated as controls and then followed for 13 wk to observe colony growth. In general, queen survivorship, and the number of eggs, larvae, and pupae observed in the microcolonies decreased with increasing irradiation dose. In the 50-, 70-, and 100-Gy treatments, the number of eggs observed was reduced by 68, 66, and 76%, respectively, compared with untreated control microcolonies. The number of larvae in the 50-, 70-, and, 100-Gy treatments was reduced by 99.6%, and only one pupa was observed in the 50-Gy treatment and none in the 70- and 100-Gy treatments during the 13-wk experiment. Queens in the 100-Gy treatment had significantly reduced longevity compared with queens in the other treatments. Radiation doses > or = 70 Gy stopped reproduction in W. auropunctata queens and should be sufficient as a phytosanitary treatment. Information from additional invasive ants in Myrmicinae and other subfamilies is needed before recommending a generic irradiation treatment for ants.

Exploitation of a high genomic mutation rate in Solenopsis invicta virus 1 to infer demographic information about its host, Solenopsis invicta.

The RNA-dependent RNA polymerase (RdRp) region of Solenopsis invicta virus 1 (SINV-1) was sequenced from 47 infected colonies of S. invicta, S. richteri, S. geminata, and S. invicta/richteri hybrids collected from across the USA, northern Argentina, and northern Taiwan in an attempt to infer demographic information about the recent S. invicta introduction into Taiwan by phylogenetic analysis. Nucleotide sequences were calculated to exhibit an overall identity of >90% between geographically-separated samples. A total of 171 nucleotide variable sites (representing 22.4% of the region amplified) were mapped across the SINV-1 RdRp alignment and no insertions or deletions were detected. Phylogenetic analysis at the nucleotide level revealed clustering of Argentinean sequences, distinct from the USA sequences. Moreover, the SINV-1 RdRp sequences derived from recently introduced populations of S. invicta from northern Taiwan resided within the multiple USA groupings implicating the USA as the source for the recent introduction of S. invicta into Taiwan. Examination of the amino acid alignment for the RdRp revealed sequence identity >98% with only nine amino acid changes observed. Seven of these changes occurred in less than 4.3% of samples, while 2 (at positions 1266 and 1285) were featured prominently. Changes at positions 1266 and 1285 accounted for 36.2% and 34.0% of the samples, respectively. Two distinct groups were observed based on the amino acid residue at position 1266, Threonine or Serine. In cases where this amino acid was a Threonine, 90% of these sequences possessed a corresponding Valine at position 1285; only 10% of the Threonine(1266)-containing sequences possessed an Isoleucine at the 1285 position. Among the Serine(1266) group, 76% possessed an Isoleucine at position 1285, while only 24% possessed a Valine. Thus, it appears that the Threonine(1266)/Valine(1285) and Serine(1266)/Isoleucine(1285) combinations are predominant phenotypes.

Ecological dominance of the red imported fire ant, Solenopsis invicta, in its native range.

Despite the widespread impacts invasive species can have in introduced populations, little is known about competitive mechanisms and dominance hierarchies between invaders and similar taxa in their native range. This study examines interactions between the red imported fire ant, Solenopsis invicta, and other above-ground foraging ants in two habitats in northeastern Argentina. A combination of pitfall traps and baits was used to characterize the ant communities, their dominance relationships, and to evaluate the effect of phorid flies on the interactions. Twenty-eight ant species coexisted with S. invicta in a gallery forest gap, whereas only ten coexisted with S. invicta in a xerophytic forest grassland. S. invicta was the most numerically dominant species in the richest and complex habitat (gallery forest); however it performed better as discoverer and dominator in the simpler habitat. S. invicta was active during day and night. In spite of its poor capacity to discover resources, S. invicta showed the highest ecological dominance and the second-best behavioral dominance after Camponotus blandus. S. invicta won 78% of the interactions with other ants, mostly against its most frequent competitor, Pheidole cf. obscurithorax, dominating baits via mass recruitment and chemical aggression. P. cf. obscurithorax was the best food discoverer. S. invicta won 80% of the scarce interactions with Linepithema humile. Crematogaster quadriformis was one of the fastest foragers and the only ant that won an equal number of contests against S. invicta. The low presence of phorid flies affected the foraging rate of S. invicta, but not the outcome of interspecific interactions. This study revealed that the red imported fire ant ecologically dominated other terrestrial ants in its native range; however, other species were able to be numerically dominant or co-dominant in its presence.

Phenology, distribution, and host specificity of Solenopsis invicta virus-1.

Studies were conducted to examine the phenology, geographic distribution, and host specificity of the Solenopsis invicta virus-1 (SINV-1). Two genotypes examined, SINV-1 and -1A, exhibited similar seasonal prevalence patterns. Infection rates among colonies of S. invicta in Gainesville, Florida, were lowest from early winter (December) to early spring (April) increasing rapidly in late spring (May) and remaining high through August before declining again in the fall (September/October). Correlation analysis revealed a significant relationship between mean monthly temperature and SINV-1 (p<0.0005, r=0.82) and SINV-1A (p<0.0001, r=0.86) infection rates in S. invicta colonies. SINV-1 was widely distributed among S. invicta populations. The virus was detected in S. invicta from Argentina and from all U.S. states examined, with the exception of New Mexico. SINV-1 and -1A were also detected in other Solenopsis species. SINV-1 was detected in Solenopsis richteri and the S. invicta/richteri hybrid collected from northern Alabama and Solenopsis geminata from Florida. SINV-1A was detected in S. geminata and Solenopsis carolinensis in Florida and the S. invicta/richteri hybrid in Alabama. Of the 1989 arthropods collected from 6 pitfall trap experiments from Gainesville and Williston, Florida, none except S. invicta tested positive for SINV-1 or SINV-1A. SINV-1 did not appear to infect or replicate within Sf9 or Dm-2 cells in vitro. The number of SINV-1 genome copies did not significantly increase over the course of the experiment, nor were any cytopathic effects observed. Phylogenetic analyses of SINV-1/-1A nucleotide sequences indicated significant divergence between viruses collected from Argentina and the U.S.

Transmission of Vairimorpha invictae (Microsporidia: Burenellidae) infections between red imported fire ant (Hymenoptera: Formicidae) colonies.

Red imported fire ant, Solenopsis invicta, colonies were successfully infected with the microsporidium Vairimorpha invictae by introducing live larvae, pupae, or dead adults from V. invictae-infected field colonies collected in Argentina. Introductions with 4th instar larvae or non-melanized pupae obtained from infected field colonies, resulted in infection of 40% of the inoculated colonies. Introductions of 4th instars or melanized pupae produced from colonies that were initially infected in the laboratory, resulted in infections of 83% of the colonies, thus perpetuating the infection in other colonies. Infection was detected in 2 of 6 colonies after introducing adult worker caste ants that had died with V. invictae. The average number of adults and the volume of immature ants per colony were significantly lower in the infected than in the control colonies. Infected colonies had 86% fewer adults per colony and 82% less immature ants than the controls. A portion of the 16S rRNA gene of the V. invictae identified from these studies was amplified, cloned, and sequenced; the 1251 nucleotide amplicon was 100% identical to the 16S rRNA gene sequence recorded previously in the GenBank database, thus verifying the species as V. invictae. This is the first report of the artificial transmission of this pathogen to uninfected ant colonies, and demonstration of its ability to hinder growth in individual colonies.