Fly connectome over the wire
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Cold metal transfer (CMT) is a pioneering feeding system widely used in wire-arc additive manufacturing (WAAM) and welding. However, process optimisation remains challenging. Although CMT has been extensively applied in various industrial sectors, its underlying mechanism is poorly understood because of the complex physics of the interactions between the wire and molten material and the wire’s highly dynamic motion. To elucidate the complexity and features of CMT, we explore the dynamic behaviour and anatomy of molten materials during wire motions (withdrawal and dipping cycles) using high-speed photography at a timescale of microseconds. We reveal a crucial driving force in the melt pool and the frequent ejection of streams or particles during CMT. This study contributes to WAAM and welding by presenting the influential features of ultra-high-dynamics CMT and facilitating the progression of process optimisation.
Neuronal polyunsaturated fatty acids are protective in ALS/FTD
Here we report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in a Drosophila model of C9orf72 repeat expansion, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), and in human postmortem ALS spinal cord. We performed lipidomics on C9 ALS/FTD Drosophila, induced pluripotent stem (iPS) cell neurons and postmortem FTD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). Feeding C9 ALS/FTD flies PUFAs yielded a modest increase in survival. However, increasing PUFA levels specifically in neurons of C9 ALS/FTD flies, by overexpressing fatty acid desaturase enzymes, led to a substantial extension of lifespan. Neuronal overexpression of fatty acid desaturases also suppressed stressor-induced neuronal death in iPS cell neurons of patients with both C9 and TDP-43 ALS/FTD. These data implicate neuronal fatty acid saturation in the pathogenesis of ALS/FTD and suggest that interventions to increase neuronal PUFA levels may be beneficial.
Macroevolution along developmental lines of least resistance in fly wings
Evolutionary change requires genetic variation, and a reigning paradigm in biology is that rates of microevolution can be predicted from estimates of available genetic variation within populations. However, the accuracy of such predictions should decay on longer evolutionary timescales, as the influence of genetic constraints diminishes. Here we show that intrinsic developmental variability and standing genetic variation in wing shape in two distantly related flies, Drosophila melanogaster and Sepsis punctum, are aligned and predict deep divergence in the dipteran phylogeny, spanning >900 taxa and 185 million years. This alignment cannot be easily explained by constraint hypotheses unless most of the quantified standing genetic variation is associated with deleterious side effects and is effectively unusable for evolution. However, phenotyping of 71 genetic lines of S. punctum revealed no covariation between wing shape and fitness, lending no support to this hypothesis. We also find little evidence for genetic constraints on the pace of wing shape evolution along the dipteran phylogeny. Instead, correlational selection related to allometric scaling, simultaneously shaping developmental variability and deep divergence in fly wings, emerges as a potential explanation for the observed alignment. This suggests that pervasive natural selection has the potential to shape developmental architectures of some morphological characters such that their intrinsic variability predicts their long-term evolution.
Genetically-encoded markers for confocal visualization of single dense core vesicles
Neuronal dense core vesicles (DCVs) store and release a diverse array of neuromodulators, trophic factors, and bioamines. The analysis of single DCVs has largely been possible only using electron microscopy, which makes understanding cargo segregation and DCV heterogeneity difficult. To address these limitations, we develop genetically encoded markers for DCVs that can be used in combination with standard immunohistochemistry and expansion microscopy to enable single-vesicle resolution with confocal microscopy in Drosophila.
A tumor-secreted protein utilizes glucagon release to cause host wasting
Tumor‒host interaction plays a critical role in malignant tumor-induced organ wasting across multiple species. Despite known regulation of regional wasting of individual peripheral organs by tumors, whether and how tumors utilize critical host catabolic hormone(s) to simultaneously induce systemic host wasting, is largely unknown. Using the conserved yki3SA-tumor model in Drosophila, we discovered that tumors increase the production of adipokinetic hormone (Akh), a glucagon-like catabolic hormone, to cause systemic host wasting, including muscle dysfunction, lipid loss, hyperglycemia, and ovary atrophy. We next integrated RNAi screening and Gal4-LexA dual expression system to show that yki3SA-gut tumors secrete Pvf1 to remotely activate its receptor Pvr in Akh-producing cells (APCs), ultimately promoting Akh production. The underlying molecular mechanisms involved the Pvf1-Pvr axis that triggers Mmp2-dependent ECM remodeling of APCs and enhances innervation from the excitatory cholinergic neurons. Interestingly, we also confirmed the similar mechanisms governing tumor-induced glucagon release and organ wasting in mammals. Blockade of either glucagon or PDGFR (homolog of Pvr) action efficiently ameliorated organ wasting in the presence of malignant tumors. Therefore, our results demonstrate that tumors remotely promote neural-associated Akh/glucagon production via Pvf1-Pvr axis to cause systemic host wasting.
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