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Spatial learning is impaired in humans with preclinical Alzheimer's disease (AD). We reported similar impairments in 3xTg-AD mice learning a spatial reorientation task. Memory reactivation during sleep is critical for learning-related plasticity, and memory consolidation is correlated with hippocampal sharp wave ripple (SWR) density, cortical delta waves (DWs), cortical spindles, and the temporal coupling of these events-postulated as physiological substrates for memory consolidation. Further, hippocampal-cortical discoordination is prevalent in individuals with AD. Thus, we hypothesized that impaired memory consolidation mechanisms in hippocampal-cortical networks could account for spatial memory deficits. We assessed sleep architecture, SWR-DW dynamics, and memory reactivation in a mouse model of tauopathy and amyloidosis implanted with a recording array targeting isocortex and hippocampus. Mice underwent daily recording sessions of rest-task-rest while learning the spatial reorientation task. We assessed memory reactivation by matching activity patterns from the approach to the unmarked reward zone to patterns during slow-wave sleep (SWS). AD mice had more SWS, but reduced SWR density. The increased SWS compensated for reduced SWR density so there was no reduction in SWR number. In control mice, spindles were phase-coupled with DWs, and hippocampal SWR-cortical DW coupling was strengthened in post-task sleep and was correlated with performance on the spatial reorientation task the following day. However, in AD mice, SWR-DW and spindle-DW coupling were impaired. Thus, reduced SWR-DW coupling may cause impaired learning in AD, and spindle-DW coupling during short rest-task-rest sessions may serve as a biomarker for early AD-related changes in these brain dynamics.

The eastern redbud, Cercis canadensis, is a small tree native to eastern North America that has become a commonly used ornamental in the United States and worldwide. We used laboratory experiments to test whether the seedpods of eastern redbuds are wind dispersed by exposing them to pulses of air blowing at different wind speeds. Rush milkweed, Asclepias subulata, seeds, which have morphological modifications that make them truly wind dispersed, were used for comparison. At all speeds tested (0, 25, 35 km/h), at a height of 190.5 cm above the ground, the seedpods of C. canadensis remained airborne much for a shorter time than the seeds of A. subulata. At all wind speeds tested, eastern redbud seedpods were minimally wind dispersed. Among all variables measured (wind speed, seedpods, mass, length, width, and area), wind speed explained approximately 0.28 (linear regression) of the seedpod dispersal. [ABSTRACT FROM AUTHOR]

This study investigated some elements of the folklore surrounding white-tailed deer hunting and determined if one or more of those elements can be scientifically falsified. To address this goal, we combined time-stamped images of moving white tailed deer, Odocoileus virginianus (Zimmermann, 1780) (Mammalia: Artiodactyla: Cervidae) generated by trigger cameras placed in a rural site in Effort, Pennsylvania, and meteorological data from an Automated Surface Observing System (ASOS) station located at the Lehigh Valley International Airport (Hanover Township, Lehigh County) some 40 km south. The only element of the hunter's myths supported is that deer tend to move more at milder temperatures (0-10ºC and 20ºC). We also found that deer move more at a slightly below normal mean sea level pressure (1013.25 mbar, 29.92 inches of mercury), during a new and full moon, and when there are calm to mild winds. [ABSTRACT FROM AUTHOR]

A strategy for pandemic preparedness is the development of antivirals against a wide set of viral targets with complementary mechanisms of action. SARS-CoV-2 nsp3-mac1 is a viral macrodomain with ADP-ribosylhydrolase activity, which counteracts host immune response. Targeting the virus' immunomodulatory functionality offers a differentiated strategy to inhibit SARS-CoV-2 compared to approved therapeutics, which target viral replication directly. Here we report a fragment-based lead generation campaign guided by computational approaches. We discover tool compounds which inhibit nsp3-mac1 activity at low nanomolar concentrations, and with responsive structure-activity relationships, high selectivity, and drug-like properties. Using our inhibitors, we show that inhibition of nsp3-mac1 increases ADP-ribosylation, but surprisingly does not translate to demonstrable antiviral activity in cell culture and iPSC-derived pneumocyte models. Further, no synergistic activity is observed in combination with interferon gamma, a main protease inhibitor, nor a papain-like protease inhibitor. Our results question the extent to which targeting modulation of innate immunity-driven ADP-ribosylation can influence SARS-CoV-2 replication. Moreover, these findings suggest that nsp3-mac1 might not be a suitable target for antiviral therapeutics development.