Attentional demands following perceptual skill training

Practicing simple visual tasks induces substantial improvement. We investigated whether increased efficiency is accompanied by automaticity and immunity to across-task interference. We found that although practice speeds orientation feature detection, it does not abolish susceptibility to interference from introduction of concurrent central-letter identification, which takes priority. Yet following training with each task, observers successfully managed to perform the tasks concurrently. The effectiveness of separate training implies that the role of improved intertask coordination in achieving concurrent performance was minor. Indeed, even when initial training was concurrent, improvement on the two tasks was sequential, and the higher-priority (central) task was learned first. However, automatic processing was not accomplished either, because increasing the difficulty of the higher-priority task interfered with performance of both tasks. What appears to be orchestrated posttraining performance i

Learning Pop-Out Detection: Building Representations for Conflicting Target-Distractor Relationships

Studies of perceptual learning consistently found that improvement is stimulus specific. These findings were interpreted as indicating an early cortical learning site. In line with this interpretation, we consider two alternative hypotheses: the `earliest modification' and the `output-level modification' assumptions, which respectively assume that learning occurs within the earliest representation which is selective for the trained stimuli, or at cortical levels receiving its output. We studied performance in a pop-out task using light bar distractor elements of one orientation, and a target element rotated by 30 (or 90). We tested the alternative hypotheses by examining pop-out learning through an initial training phase, a subsequent learning stage with swapped target and distractor orientations, and a final re-test with the originally trained stimuli. We found learning does not transfer across orientation swapping. However, following training with swapped orientations, a similar performance level is reached as with original orientations. That is, learning neither facilitates nor interferes to a substantial degree with subsequent performance with altered stimuli. Furthermore, this re-training does not hamper performance with the originally trained stimuli. If training changed the earliest orientation selective representation (specializing it for performance of the particular performed task) it would necessarily affect performance with swapped orientations, as well. The co-existence of similar asymptotes for apparently conflicting stimulus sets refutes the `earliest modification' hypothesis, supporting the alternative `output level modification' hypothesis. We conclude that secondary cortical processing levels use outputs from the earliest orientation representation to ..

Induction of karyopherin α1 expression by indole-3-acetic acid in auxin-treated or overproducing tobacco plants

Macromolecules may transfer between the cytoplasm and the nucleus only through specific gates—the nuclear pore complexes (NPCs). Translocation of nucleic acids and large proteins requires the presence of a nuclear localization signal (NLS) within the transported molecule. This NLS is recognized by a class of soluble transport receptors termed karyopherins α and β. We previously characterized the expression pattern of the tomato karyopherin α1 (LeKAPα1) promoter in transformed tobacco plants. Expression of LeKAPα1 was mainly observed in growing tissues where cell division and extension is rapid. The expression pattern of LeKAPα1 resembled that of auxin-responsive genes. This led us to suggest that auxin participates in the regulation of LeKAPα1 expression. Here we characterized the correlation between auxin level and the activity of the LeKAPα1 promoter. To this end, transgenic tobacco plants carrying the GUS reporter gene under the control of the LeKAPα1 promoter were treated with various levels of exogenous auxin. We also studied transgenic plants in which we increased the endogenous levels of auxin. For this, we expressed in plants both the LeKAPα1 promoter-GUS reporter and the Agrobacterium tumefaciens iaaM gene, which increases the endogenous levels of auxin. The results indicate that the auxin indole-3-acetic acid (IAA) can induce LeKAPα1 expression. We also identified that the sites and levels of LeKAPα1 expression correlated with the endogenous pathways of polar auxin transport

From a genome-wide screen of RNAi molecules against SARS-CoV-2 to a validated broad-spectrum and potent prophylaxis.

Funder: Bill and Melinda Gates FoundationExpanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen of over 16,000 RNAi triggers against the SARS-CoV-2 genome, using a massively parallel assay to identify hyper-potent siRNAs. We selected Ten candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity (IC50 < 20 pM) and strong blockade of infectivity in live-virus experiments. We further enhanced this activity by combinatorial pairing of the siRNA candidates and identified cocktails that were active against multiple types of variants of concern (VOC). We then examined over 2,000 possible mutations in the siRNA target sites by using saturation mutagenesis and confirmed broad protection of the leading cocktail against future variants. Finally, we demonstrated that intranasal administration of this siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the gold-standard Syrian hamster model. Our results pave the way for the development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies

From a genome-wide screen of RNAi molecules against SARS-CoV-2 to a validated broad-spectrum and potent prophylaxis.

Acknowledgements: This study was funded in part by the Bill & Melinda Gates Foundation and by the intramural program of the National Institutes of Health. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. This work was conducted in part under CRADA 2020-0597 between the VRC/NIAID and Eleven Therapeutics. Some of the work was funded by research grants to I.G. from Wellcome Trust, reference no. 207498/Z/17/Z and MRC/UKRI G2P-UK National Virology consortium, reference no. MR/W005611/1. I.G. is a Wellcome Trust Senior Fellow.Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation); doi: https://doi.org/10.13039/100000865Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen of over 16,000 RNAi triggers against the SARS-CoV-2 genome, using a massively parallel assay to identify hyper-potent siRNAs. We selected Ten candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity (IC50 < 20 pM) and strong blockade of infectivity in live-virus experiments. We further enhanced this activity by combinatorial pairing of the siRNA candidates and identified cocktails that were active against multiple types of variants of concern (VOC). We then examined over 2,000 possible mutations in the siRNA target sites by using saturation mutagenesis and confirmed broad protection of the leading cocktail against future variants. Finally, we demonstrated that intranasal administration of this siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the gold-standard Syrian hamster model. Our results pave the way for the development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies