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Through three experiments, we examined older and younger adults’ metacognitive ability to distinguish between what is not stored in the knowledge base versus merely inaccessible. Difficult materials were selected to test this ability when retrieval failures were very frequent. Of particular interest was the influence of feedback (and lack thereof) in potential new learning and recovery of marginal knowledge across age groups. Participants answered short-answer general knowledge questions, responding “I do not know” (DK) or “I do not remember” (DR) when retrieval failed. After DKs, performance on a subsequent multiple-choice (Exp. 1) and short-answer test following correct-answer feedback (Exp. 2) was lower than after DRs, supporting self-reported not remembering reflects failures of accessibility whereas not knowing captures a lack of availability. Yet, older adults showed a tendency to answer more DK questions correctly on the final tests than younger adults. Experiment 3 was a replication and extension of Experiment 2 including two groups of online participants in which one group was not provided correct answer feedback during the initial short-answer test. This allowed us to examine the degree to which any new learning and recovery of access to marginal knowledge was occurring across the age groups. Together, the findings indicate that (1) metacognitive awareness regarding underlying causes of retrieval failures is maintained across different distributions of knowledge accessibility, (2) older adults use correct answer feedback more effectively than younger adults, and (3) in the absence of feedback, older adults spontaneously recover marginal knowledge.

Recombinant adeno-associated virus (rAAV) has been widely used as a viral vector across mammalian biology and has been shown to be safe and effective in human gene therapy. We demonstrate that neural progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are particularly sensitive to rAAV-induced cell death. Cell loss is dose dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with loss of BrdU-labeled cells within 18 hr post-injection and no evidence of recovery of adult neurogenesis at 3 months post-injection. The remaining mature DGCs appear hyperactive 4 weeks post-injection based on immediate early gene expression, consistent with previous studies investigating the effects of attenuating adult neurogenesis. In vitro application of AAV or electroporation of AAV2 inverted terminal repeats (ITRs) is sufficient to induce cell death. Efficient transduction of the dentategyrus (DG)– without ablating adult neurogenesis– can be achieved by injection of rAAV2-retro serotyped virus into CA3. rAAV2-retro results in efficient retrograde labeling of mature DGCs and permits in vivo two-photon calcium imaging of dentate activity while leaving adult neurogenesis intact. These findings expand on recent reports implicating rAAV-linked toxicity in stem cells and other cell types and suggest that future work using rAAV as an experimental tool in the DG and as a gene therapy for diseases of the central nervous system should be carefully evaluated.

Polar ecosystems are sensitive to climate forcing, and we often lack baselines to evaluate changes. Here we report a nearly 50-year study in which a sudden shift in the population dynamics of an ecologically important, structure-forming hexactinellid sponge, Anoxycalyx joubini was observed. This is the largest Antarctic sponge, with individuals growing over two meters tall. In order to investigate life history characteristics of Antarctic marine invertebrates, artificial substrata were deployed at a number of sites in the southern portion of the Ross Sea between 1967 and 1975. Over a 22-year period, no growth or settlement was recorded for A. joubini on these substrata; however, in 2004 and 2010, A. joubini was observed to have settled and grown to large sizes on some but not all artificial substrata. This single settlement and growth event correlates with a region-wide shift in phytoplankton productivity driven by the calving of a massive iceberg. We also report almost complete mortality of large sponges followed over 40 years. Given our warming global climate, similar system-wide changes are expected in the future.