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Abstract Neurons deploy diverse adaptive strategies to ensure survival and neurotransmission amid cellular stress. When these adaptive pathways are overwhelmed, functional impairment or neurodegeneration follows. Here we show that stressed neurons actively induce a state of transmissive dormancy as a protective measure. Extending observations of neurotrauma in C. elegans and mice, human dopaminergic neurons capable of surviving severe cellular challenges both decrease spontaneous activity and modulate dopamine homeostasis through the transcriptional regulator Yin Yang 1 (YY1). To bolster stress resilience and mitigate dopamine toxicity, YY1 increases expression of the vesicular monoamine transporter 2, vMAT2, while coordinately inhibiting dopamine synthesis through stabilization of a guanine quadruplex in intron 10 of tyrosine hydroxylase, TH. This dopaminergic stress response has the potential to cause circuit inactivation, yet safeguards neurons by minimizing the toxic accumulation of cytosolic dopamine and inducing a state of neuronal dormancy. In essence, neurons appear to actively prioritize viability over functionality.

Abstract Protein fibril self-assembly is a universal transition implicated in neurodegenerative diseases. Although fibril structure/growth are well characterized, fibril nucleation is poorly understood. Here, we use a computational-experimental approach to resolve fibril nucleation. We show that monomer hairpin content quantified from molecular dynamics simulations is predictive of experimental fibril formation kinetics across a tau motif mutant library. Hairpin trimers are predicted to be fibril transition states; one hairpin spontaneously converts into the cross-beta conformation, templating subsequent fibril growth. We designed a disulfide-linked dimer mimicking the transition state that catalyzes fibril formation, measured by ThT fluorescence and TEM, of wild-type motif - which does not normally fibrillize. A dimer compatible with extended conformations but not the transition-state fails to nucleate fibril at any concentration. Tau repeat domain simulations show how long-range interactions sequester this motif in a mutation-dependent manner. This work implies that different fibril morphologies could arise from disease-dependent hairpin seeding from different loci.

The authors used multi-disciplinary approaches to understand the structural mechanism underlying spontaneous aggregation of tau encoding an S320F FTD-tau mutant. Understanding the mechanisms of tau aggregation will help identify novel methods to regulate its misfolding.

Although agricultural intensification has been linked with the increment of lake eutrophication and shallow lake research has demonstrated the importance of submerged macrophytes for maintaining water clarity, less is known about the role of macrophytes and the effects of agriculture on shallow lakes of the global south. Shallow lakes in the Pampean region of Argentina are subjected to high anthropic pressure and are classified as eutrophic and hypereutrophic and, in spite of most of them are turbid and dominated by phytoplankton biomass, some remain in a clear-vegetated regime with profuse submerged macrophytes. We studied the potential drivers of phytoplankton biomass (estimated as Chlorophyll-a - Chla) by applying a regional approach and a model selection process for a dataset of 58 shallow lakes that represent the variability of the Pampean region. For the 58 lakes, the presence of submerged macrophytes, total nitrogen, and nearby agriculture of each lake were the main drivers of Chla with −1.55, 0.19 and 0.02 coefficient values, respectively. Moreover, a high proportion of the variance in this dataset (37.7 %) was explained by the regional location of each lake (hydrographic systems). For lakes with macrophytes (N = 8), Chla exhibited a positive relationship with total phosphorus (coefficient value = 3.05), whereas for lakes without macrophytes (N = 50) Chla showed a positive relationship with nearby agricultural development (coefficient value = 0.02) and 36.4 % of variance explained by the hydrographic system. Our regional approach highlighted the importance of submerged macrophytes in shaping phytoplankton biomass in Pampean shallow lakes. Our results support the idea that the conservation of submerged macrophytes, as well as the control of agriculture in the riparian zones of lakes, will help to stabilize the shallow lakes in clear regime, even in regions highly impacted by agriculture and in lakes under eutrophic conditions.

Submerged macrophytes play a key role in maintaining clear vegetated states in shallow lakes, but their role on methane (CH4) dynamics is less explored. They might enhance methanogenesis by providing organic matter but they can also supply oxygen to the sediments increasing methanotrophy. They may also affect gas exchange by diminishing wind turbulence in the water column. We previously measured seasonal CO2 and CH4 partial pressure (pCO2 and pCH4) and diffusive fluxes from two clear vegetated and two turbid algal shallow lakes of the Pampean Plain, Argentina, and we reported that clear lakes had higher mean annual pCH4 despite states having similar mean annual CH4 diffusive flux. In this study we explore the contribution of physical and biological factors regulating surface pCH4. Mean annual CH4 diffusive fluxes and CH4 fraction of oxidation (Fox) were similar between states, implying a comparable mean annual CH4 input. kCH4 was significantly higher than kCO2, suggesting occurrence of CH4 microbubbles, yet kCH4 was higher in turbid lakes than in clear lakes, implying a higher microbubble formation in turbid lakes. Furthermore, in turbid lakes there were positive relationships between k and wind speed, and between k and pCH4, yet in clear lakes these relations were absent. Results suggest that submerged vegetation suppresses wind induced turbulence in clear vegetated lakes, decoupling kCH4 from wind and reducing microbubble formation, therefore augmenting pCH4 in their surface waters. Overall, physical rather than biological factors appear to control the observed differences in pCH4 between states.