Viscous Cross-waves: An Analytical Treatment

Viscous effects on the excitation of cross‐waves in a semi‐infinite box of finite depth and width are considered. A formalism using matched asymptotic expansions and an improved method of computing the solvability condition is used to derive the relative contributions of the free‐surface, sidewall, bottom, and wavemaker viscous boundary layers. This analysis yields an expression for the damping coefficient previously incorporated on heuristic grounds. In addition, three new contributions are found: a viscous detuning of the resonant frequency, a slow spatial variation in the coupling to the progressive wave, and a viscous correction to the wavemaker boundary condition. The wavemaker boundary condition breaks the symmetry of the linear neutral stability curve at leading order for many geometries of experimental interest

Conditioned inhibition and reinforcement rate

We investigated conditioned inhibition in a magazine approach paradigm. Rats were trained on a feature negative discrimination between an auditory conditioned stimulus (CS) reinforced at one rate versus a compound of that CS and a visual stimulus (L) reinforced at a lower rate. This training established L as a conditioned inhibitor. We then tested the inhibitory strength of L by presenting it in compound with other auditory CSs. L reduced responding when tested with a CS that had been reinforced at a high rate, but had less or even no inhibitory effect when tested with a CS that had been reinforced at a low rate. The inhibitory strength of L was greater if it signaled a decrease in reinforcement from an already low rate than if it signaled an equivalent decrease in reinforcement from a high rate. We conclude that the strength of inhibition is not a linear function of the change in reinforcement that it signals. We discuss the implications of this finding for models of learning (e.g. Rescorla & Wagner, 1972) that identify inhibition with a difference (subtraction) rule.Australian Research Counci

Magazine approach during a signal for food depends on Pavlovian, not instrumental, conditioning

In the conditioned magazine approach paradigm, rats are exposed to a contingent relationship between a conditioned stimulus (CS) and the delivery of food (the unconditioned stimulus, US). As the rats learn the CS-US association, they make frequent anticipatory head entries into the food magazine (the conditioned response, CR) during the CS. Conventionally, this is considered to be a Pavlovian paradigm because food is contingent on the CS and not on the performance of CRs during the CS. However, because magazine entries during the CS are reliably followed by food, the increase in frequency of those responses may involve adventitious (“superstitious”) instrumental conditioning. The existing evidence, from experiments using an omission schedule to eliminate the possibility of instrumental conditioning (Farwell & Ayres, 1979; Holland, 1979), is ambiguous: rats acquire magazine CRs despite the omission schedule, demonstrating that the response does not depend on instrumental conditioning, but the response rate is greatly depressed compared with that of rats trained on a yoked schedule, consistent with a contribution from instrumental conditioning under normal (non-omission) schedules. Here we describe experiments in which rats were trained on feature-positive or feature-negative type discriminations between trials that were reinforced on an omission schedule versus trials reinforced on a yoked schedule. The experiments show that the difference in responding between omission and yoked schedules is due to suppression of responding under the omission schedule rather than an elevation of responding under the yoked schedule. We conclude that magazine responses during the CS are largely or entirely Pavlovian CRs.Australian Research Council: Grant DP109269

Semi-quantitative mass spectrometry in AML cells identifies new non-genomic targets of the EZH2 methyltransferase

Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all-transretinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML

Sharing voxelwise neuroimaging results from rhesus monkeys and other species with Neurovault

© 2020 The Authors Animal neuroimaging studies can provide unique insights into brain structure and function, and can be leveraged to bridge the gap between animal and human neuroscience. In part, this power comes from the ability to combine mechanistic interventions with brain-wide neuroimaging. Due to their phylogenetic proximity to humans, nonhuman primate neuroimaging holds particular promise. Because nonhuman primate neuroimaging studies are often underpowered, there is a great need to share data amongst translational researchers. Data sharing efforts have been limited, however, by the lack of standardized tools and repositories through which nonhuman neuroimaging data can easily be archived and accessed. Here, we provide an extension of the Neurovault framework to enable sharing of statistical maps and related voxelwise neuroimaging data from other species and template-spaces. Neurovault, which was previously limited to human neuroimaging data, now allows researchers to easily upload and share nonhuman primate neuroimaging results. This promises to facilitate open, integrative, cross-species science while affording researchers the increased statistical power provided by data aggregation. In addition, the Neurovault code-base now enables the addition of other species and template-spaces. Together, these advances promise to bring neuroimaging data sharing to research in other species, for supplemental data, location-based atlases, and data that would otherwise be relegated to a file-drawer . As increasing numbers of researchers share their nonhuman neuroimaging data on Neurovault, this resource will enable novel, large-scale, cross-species comparisons that were previously impossible

Perturbation of Retinoid Homeostasis Increases Malformation Risk in Embryos Exposed to Pregestational Diabetes

Funding. This work was supported by funding from Hong Kong Research Grants Council General Research Fund project reference 441606 and 474109 to A.S.W.S., Y.C.L., C.C.W., P.J.M. and A.J.C..Peer reviewedPostprin