Meta-analysis of honey bee neurogenomic response links deformed wing virus type A to precocious behavioral maturation

Crop pollination by the western honey bee Apis mellifera is vital to agriculture but threatened by alarmingly high levels of colony mortality, especially in Europe and North America. Colony loss is due, in part, to the high viral loads of Deformed wing virus (DWV), transmitted by the ectoparasitic mite Varroa destructor, especially throughout the overwintering period of a honey bee colony. Covert DWV infection is commonplace and has been causally linked to precocious foraging, which itself has been linked to colony loss. Taking advantage of four brain transcriptome studies that unexpectedly revealed evidence of covert DWV-A infection, we set out to explore whether this effect is due to DWV-A mimicking naturally occurring changes in brain gene expression that are associated with behavioral maturation. Consistent with this hypothesis, we found that brain gene expression profiles of DWV-A infected bees resembled those of foragers, even in individuals that were much younger than typical foragers. In addition, brain transcriptional regulatory network analysis revealed a positive association between DWV-A infection and transcription factors previously associated with honey bee foraging behavior. Surprisingly, single-cell RNA-Sequencing implicated glia, not neurons, in this effect; there are relatively few glial cells in the insect brain and they are rarely associated with behavioral plasticity. Covert DWV-A infection also has been linked to impaired learning, which together with precocious foraging can lead to increased occurrence of infected bees from one colony mistakenly entering another colony, especially under crowded modern apiary conditions. These findings provide new insights into the mechanisms by which DWV-A affects honey bee health and colony survival

Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

Parkinson’s disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson’s disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology

Hypertrophic olivary degeneration and palatal myoclonus from a Streptococcus intermedius infection of the brain: illustrative case

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare condition that can occur after disruption of the Guillain-Mollaret triangle. Clinically, HOD can present with palatal myoclonus with or without oculopalatal tremor, which sometimes results in symptomatic dysphagia and/or speech abnormalities. This condition is commonly associated with vascular lesions, with only three prior reported cases of HOD resulting from intracranial abscess. OBSERVATIONS: An otherwise healthy patient developed multiple intracranial abscesses. Biopsy showed gram-positive cocci; however, culture findings were negative. Polymerase chain reaction (PCR) identified Streptococcus intermedius. The patient demonstrated palatal myoclonus and vertical nystagmus, which resulted in persistent mild dysphagia and altered speech intonation. After appropriate antimicrobial therapy with resolution of the enhancing lesions, symptoms persisted. Follow-up imaging demonstrated progressive hypertrophy of the right olive with persistent disruption of the right-sided rubro-olivo fiber pathways. LESSONS: Although HOD classically occurs after vascular insult, it can also be seen as a postinfectious sequela. Despite eradication of the infection, palatal myoclonus and oculopalatal tremor may have a persistent impact on quality of life due to impaired speech and swallowing. This case emphasizes the utility of universal PCR in detecting fastidious organisms as well as diffusion tensor imaging for characterization of disrupted fiber pathways

Dysregulation of Glucagon Secretion by Hyperglycemia-Induced Sodium-Dependent Reduction of ATP Production

© 2018 The Author(s). Published by Elsevier Inc.Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their β cells (Fh1βKO mice) develop progressive hyperglycemia and dysregulated glucagon secretion similar to that seen in diabetic patients (too much at high glucose and too little at low glucose). The glucagon secretion defects are corrected by low concentrations of tolbutamide and prevented by the sodium-glucose transport (SGLT) inhibitor phlorizin. These data link hyperglycemia, intracellular Na+ accumulation, and acidification to impaired mitochondrial metabolism, reduced ATP production, and dysregulated glucagon secretion. Protein succination, reflecting reduced activity of fumarase, is observed in α cells from hyperglycemic Fh1βKO and β-V59M gain-of-function KATP channel mice, diabetic Goto-Kakizaki rats, and patients with type 2 diabetes. Succination is also observed in renal tubular cells and cardiomyocytes from hyperglycemic Fh1βKO mice, suggesting that the model can be extended to other SGLT-expressing cells and may explain part of the spectrum of diabetic complications.Peer reviewe

Zero modes in a system of Aharonov-Bohm fluxes

We study zero modes of two-dimensional Pauli operators with Aharonov--Bohm fluxes in the case when the solenoids are arranged in periodic structures like chains or lattices. We also consider perturbations to such periodic systems which may be infinite and irregular but they are always supposed to be sufficiently scarce

An unexpected disruption of the atmospheric quasi-biennial oscillation

One of the most repeatable phenomena seen in the atmosphere, the quasi-biennial oscillation (QBO) between prevailing eastward and westward wind jets in the equatorial stratosphere (approximately 16 to 50 kilometers altitude), was unexpectedly disrupted in February 2016. An unprecedented westward jet formed within the eastward phase in the lower stratosphere and cannot be accounted for by the standard QBO paradigm based on vertical momentum transport. Instead, the primary cause was waves transporting momentum from the Northern Hemisphere. Seasonal forecasts did not predict the disruption, but analogous QBO disruptions are seen very occasionally in some climate simulations. A return to more typical QBO behavior within the next year is forecast, although the possibility of more frequent occurrences of similar disruptions is projected for a warming climate

Intramuscular tendon injury is not associated with an increased hamstring reinjury rate within 12 months after return to play

Background Acute hamstring injury that includes intramuscular tendon injury has been suggested to be associated with increased reinjury risk. These observations were based on a relatively small number of retrospectively analysed cases. Objective To determine whether intramuscular tendon injury is associated with higher reinjury rates in acute hamstring injury. Methods MRIs of 165 athletes with an acute hamstring injury were obtained within 5 days of injury. Treatment consisted of a standardised criteria-based rehabilitation programme. Standardised MRI parameters and intramuscular tendon injury, the latter subdivided into tendon disruption and waviness, were scored. We prospectively recorded reinjuries, defined as acute onset of posterior thigh pain in the same leg within 12 months after return to play. Results Participants were predominantly football players (72%). Sixty-four of 165 (39%) participants had an index injury with intramuscular hamstring tendon disruption, and waviness was present in 37 (22%). In total, there were 32 (19%) reinjuries. There was no significant difference (HR: 1.05, 95% CI 0.52 to 2.12, P=0.898) in reinjury rate between index injuries with intramuscular tendon disruption (n=13, 20%) and without tendon disruption (n=19, 20%). There was no significant difference in reinjury rate (X&(1)=0.031, P=0.861) between index injuries with presence of waviness (n=7, 19%) and without presence of waviness (n=25, 20%). Conclusion In athletes with an acute hamstring injury, intramuscular tendon injury was not associated with an increased reinjury rate within 12 months after return to play