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Neural circuit function depends on the pattern of synaptic connections between neurons and the strength of those connections. Synaptic strength is determined by both postsynaptic sensitivity to neurotransmitter and the presynaptic probability of action potential evoked transmitter release (Pr). Whereas morphology and neurotransmitter receptor number indicate postsynaptic sensitivity, presynaptic indicators and the mechanism that sets Pr remain to be defined. To address this, we developed QuaSOR, a super-resolution method for determining Pr from quantal synaptic transmission imaging at hundreds of glutamatergic synapses at a time. We mapped the Pr onto super-resolution 3D molecular reconstructions of the presynaptic active zones (AZs) of the same synapses at the Drosophila larval neuromuscular junction (NMJ). We find that Pr varies greatly between synapses made by a single axon, quantify the contribution of key AZ proteins to Pr diversity and find that one of these, Complexin, suppresses spontaneous and evoked transmission differentially, thereby generating a spatial and quantitative mismatch between release modes. Transmission is thus regulated by the balance and nanoscale distribution of release-enhancing and suppressing presynaptic proteins to generate high signal-to-noise evoked transmission.

BackgroundCopper associated hepatitis (CAH) has been increasingly recognized in dogs, and speculation exists that hereditary defects in copper metabolism have been exacerbated by increased environmental copper exposure. However, no broad epidemiological investigations have been performed to investigate quantitative hepatic copper concentrations ([Cu]H ) over time in both dogs that are (predisposed breed [PB]), and are not (non-predisposed breed [NPB]), considered at-risk for CAH.ObjectivesTo investigate [Cu]H in dogs and explore temporal, demographic, and histologic associations spanning 34 years.Animals546 archived liver specimens.MethodsRetrospective study. Searches of the Michigan State University Veterinary Diagnostic Laboratory database identified dogs that had undergone hepatic histopathologic assessment. Cases with archived tissue were reviewed and classified by breed, time period, and presence or absence of hepatitis. Inductively coupled plasma mass spectrometry was used to determine [Cu]H .ResultsIn time period 2009-2015, median [Cu]H were 101 μg/g and 313 μg/g greater than median [Cu]H in time period 1982-1988 for NPB and PB dogs, respectively (P < .001 for both comparisons). The proportion of dogs with [CU]H > 300 μg/g increased in NPB (28% to 49%) and PB dogs (48% to 71%) during these periods (P = .002 for both comparisons). Median [Cu]H in dogs with hepatitis increased 3-fold over time in both NPB (P = .004) and PB populations (P < .001).Conclusions and clinical importanceThe frequent recognition of CAH in recent years is likely due to the observed increases in [Cu]H over time. Importantly, effects are not limited to PB dogs.

This article discusses the phenomenon of induced seismicity, which refers to the human-caused generation of tremors and seismic events that alter the state of subsurface stresses. The occurrence of induced seismicity during subsurface technologies, such as shale gas development and renewable energy extraction, can lead to project delays and concerns about safety and environmental impact. The article highlights the need to understand the mechanisms of induced seismicity and develop strategies to minimize its effects. It presents a collection of research papers that explore fluid-induced seismicity in various energy production and storage technologies, offering insights into the interplay between fluid injection, fault behavior, and subsurface structures. The findings contribute to evidence-based policymaking and regulatory processes, supporting the development of sustainable subsurface operations for renewable energy and decarbonization technologies. [Extracted from the article]

The largest magnitude earthquake in a sequence is often used as a proxy for hazard estimates, as consequences are often predominately from this single event (in small seismic zones). In this article, the concept of order statistics is adapted to infer the maximum magnitude (MMAX) of an earthquake catalogue. A suite tools developed here can discern MMAX influences through hypothesis testing, quantify MMAX through maximum likelihood estimation (MLE) or select the best MMAX prediction amongst several models. The efficacy of these tools is benchmarked against synthetic and real-data tests, demonstrating their utility. Ultimately, 13 cases of induced seismicity spanning wastewater disposal, hydraulic fracturing and enhanced geothermal systems are tested for volume-based MMAX. I find that there is no evidence of volume-based processes influencing any of these cases. On the contrary, all these cases are adequately explained by an unbounded magnitude distribution. This is significant because it suggests that induced earthquake hazards should also be treated as unbounded. On the other hand, if bounded cases exist, then the tools developed here will be able to discern them, potentially changing how an operator mitigates these hazards. Overall, this suite of tools will be important for better-understanding earthquakes and managing their risks. This article is part of the theme issue 'Induced seismicity in coupled subsurface systems'. [ABSTRACT FROM AUTHOR]