Elevated sleep quota in a stress-resilient Drosophila species.

Sleep is broadly conserved across the animal kingdom but can vary widely between species. It is currently unclear which selective pressures and regulatory mechanisms influence differences in sleep between species. The fruit fly Drosophila melanogaster has become a successful model system for examining sleep regulation and function, but little is known about the sleep patterns in many related fly species. Here, we find that fly species with adaptations to extreme desert environments, including D. mojavensis, exhibit strong increases in baseline sleep compared with D. melanogaster. Long-sleeping D. mojavensis show intact homeostasis, indicating that desert flies carry an elevated drive for sleep. In addition, D. mojavensis exhibit altered abundance or distribution of several sleep/wake-related neuromodulators and neuropeptides that are consistent with their reduced locomotor activity and increased sleep. Finally, we find that in a nutrient-deprived environment, the sleep patterns of individual D. mojavensis are strongly correlated with their survival time and that disrupting sleep via constant light stimulation renders D. mojavensis more sensitive to starvation. Our results demonstrate that D. mojavensis is a novel model for studying organisms with high sleep drive and for exploring sleep strategies that provide resilience in extreme environments.

Elevated sleep need in a stress-resilient Drosophila species.

Sleep is broadly conserved across the animal kingdom, but can vary widely between species. It is currently unclear which types of selective pressures and sleep regulatory mechanisms influence differences in sleep between species. The fruit fly Drosophila melanogaster has become a successful model system for examining sleep regulation and function, but little is known about the sleep patterns and need for sleep in many related fly species. Here, we find that Drosophila mojavensis, a fly species that has adapted to extreme desert environments, exhibits strong increases in sleep compared to D. melanogaster. Long-sleeping D. mojavensis show intact sleep homeostasis, indicating that these flies carry an elevated need for sleep. In addition, D. mojavensis exhibit altered abundance or distribution of several sleep/wake related neuromodulators and neuropeptides that are consistent with their reduced locomotor activity, and increased sleep. Finally, we find that in a nutrient-deprived environment, the sleep responses of individual D. mojavensis are correlated with their survival time. Our results demonstrate that D. mojavensis is a novel model for studying organisms with high sleep need, and for exploring sleep strategies that provide resilience in extreme environments.

Improved Chromatography and MS-Based Detection of Glyphosate and Aminomethylphosphonic Acid Using iTrEnDi.

Glyphosate (GLY), a synthetic, nonselective systemic herbicide that is particularly effective against perennial weeds, is the most used weedkiller in the world. There are growing concerns over GLY accumulation in the environment and the attendant human health-associated risks, and despite increased attention in the media, GLY and its breakdown product aminomethylphosphonic acid (AMPA) remain elusive to many analytical strategies. Chemical derivatization coupled with high-performance liquid chromatography-mass spectrometry (HPLC-MS) addresses the challenge of quantifying low levels of GLY and AMPA in complex samples. Here we demonstrate the use of in situ trimethylation enhancement using diazomethane (iTrEnDi) to derivatize GLY and AMPA into permethylated products ([GLYTr]+ and [AMPATr]+, respectively) prior to analysis via HPLC-MS. iTrEnDi produced quantitative yields and resulted in a 12-340-fold increases in HPLC-MS-based sensitivity for [GLYTr]+ and [AMPATr]+, respectively, compared with underivatized counterparts. The limits of detection of derivatized compounds were found to be 0.99 ng/L for [GLYTr]+ and 1.30 ng/L for [AMPATr]+, demonstrating significant sensitivity improvements compared to previously established derivatization techniques. iTrEnDi is compatible with the direct derivatization of Roundup formulations. Finally, as proof of principle, a simple aqueous extraction followed by iTrEnDi enabled the detection of [GLYTr]+ and [AMPATr]+ on the exterior of field-grown soybeans that were sprayed with Roundup. Overall, iTrEnDi ameliorates issues relating to low proton affinity and chromatographic retention, boosting HPLC-MS-based sensitivity and enabling the elucidation of elusive analytes such as GLY and AMPA within agricultural systems.

Small molecules disaggregate alpha-synuclein and prevent seeding from patient brain-derived fibrils.

The amyloid aggregation of alpha-synuclein within the brain is associated with the pathogenesis of Parkinson's disease (PD) and other related synucleinopathies, including multiple system atrophy (MSA). Alpha-synuclein aggregates are a major therapeutic target for treatment of these diseases. We identify two small molecules capable of disassembling preformed alpha-synuclein fibrils. The compounds, termed CNS-11 and CNS-11g, disaggregate recombinant alpha-synuclein fibrils in vitro, prevent the intracellular seeded aggregation of alpha-synuclein fibrils, and mitigate alpha-synuclein fibril cytotoxicity in neuronal cells. Furthermore, we demonstrate that both compounds disassemble fibrils extracted from MSA patient brains and prevent their intracellular seeding. They also reduce in vivo alpha-synuclein aggregates in C. elegans. Both compounds also penetrate brain tissue in mice. A molecular dynamics-based computational model suggests the compounds may exert their disaggregating effects on the N terminus of the fibril core. These compounds appear to be promising therapeutic leads for targeting alpha-synuclein for the treatment of synucleinopathies.

Partial caecal necrosis - a rare cause of right-sided inferior abdominal pain and tenderness.

INTRODUCTION: Non-occlusive caecal infarction is a rare condition that has been described in association with a variety of clinical entities, generally due to a low-flow state, and has been reported to occur in association with chronic heart disease, open-heart surgery, certain drugs, and haemodialysis. The aim of this article is to describe the presentation, diagnosis and management of this unusual clinical problem. CASE PRESENTATION: We report on an 84-year-old female with known chronic heart disease presenting with right lower abdominal quadrant pain, tenderness and leukocytosis. Although initial clinical findings were highly suggestive of acute appendicitis, CT revealed marked circumferential wall thickening of the caecum. Intraoperatively, caecal necrosis was confirmed, while the appendix and the remainder of the intestine appeared normal. There was no evidence of major vascular occlusion or embolization. The right hemicolectomy was performed with ileo-transverse anastomosis. Histopathologic analysis demonstrated isolated transmural caecal necrosis with marked infiltration of the caecal wall by numerous bacteria and neutrophils as a consequence of nonocclusive ischaemic colitis. The patient recovered completely and was discharged from the hospital on the tenth postoperative day without any surgical complications. CONCLUSION: Partial caecal necrosis should be included in the differential diagnosis of acute right lower quadrant pain, especially in elderly patients with chronic heart disease.