Computational models, behavioral data, and electrophysiological data suggest that the CA3 subregion of the hippocampus may support multiple mnemonic processes critical to the formation and subsequent ...retrieval of spatial memories. Multiple researchers have proposed that the CA3 subregion contains an autoassociative network in which synaptic connections between CA3 neurons that represent different components of a memory are strengthened via recurrent collateral connections. As a result, it has been suggested that the CA3 autoassociative network may support multiple processes including the formation of spatial arbitrary associations, temporary maintenance of spatial working memory, and spatial pattern completion. In addition, the CA3 subregion has been suggested to be involved in spatial pattern separation. The separation of patterns is hypothesized to be accomplished based on the low probability that any two CA3 neurons will receive mossy-fiber input synapses from a similar subset of dentate gyrus cells. The separation of patterns also may be enhanced by competitive inhibition within CA3 and dentate gyrus. This review will focus on the mnemonic processes supported by CA3 neurons and how these processes may facilitate the encoding and retrieval of spatial information. Although there is growing evidence indicating that the hippocampus plays a role in the processing of nonspatial information as well, the scope of the present review will focus on the role of the CA3 subregion in spatial memory.
Young and nondemented older adults were tested on a continuous recognition memory task requiring visual pattern separation. During the task, some objects were repeated across trials and some objects, ...referred to as lures, were presented that were similar to previously presented objects. The lures resulted in increased interference and an increased need for pattern separation. For each object, the participant was asked to indicate whether (1) this was the first time the object was seen (new), (2) the object was seen previously (old), or (3) the object was similar to a previous object (similar). Older adults were able to correctly identify objects as old or new as well as young adults; however, older adults were impaired when identifying lures as similar. Therefore, pattern separation may be less efficient in older adults resulting in poorer recognition memory performance when interference is increased. (Contains 2 figures and 1 table.)
Artificial spin ice is a class of lithographically created arrays of interacting ferromagnetic nanometre-scale islands. It was introduced to investigate many-body phenomena related to frustration and ...disorder in a material that could be tailored to precise specifications and imaged directly. Because of the large magnetic energy scales of these nanoscale islands, it has so far been impossible to thermally anneal artificial spin ice into desired thermodynamic ensembles; nearly all studies of artificial spin ice have either treated it as a granular material activated by alternating fields or focused on the as-grown state of the arrays. This limitation has prevented experimental investigation of novel phases that can emerge from the nominal ground states of frustrated lattices. For example, artificial kagome spin ice, in which the islands are arranged on the edges of a hexagonal net, is predicted to support states with monopolar charge order at entropies below that of the previously observed pseudo-ice manifold. Here we demonstrate a method for thermalizing artificial spin ices with square and kagome lattices by heating above the Curie temperature of the constituent material. In this manner, artificial square spin ice achieves unprecedented thermal ordering of the moments. In artificial kagome spin ice, we observe incipient crystallization of the magnetic charges embedded in pseudo-ice, with crystallites of magnetic charges whose size can be controlled by tuning the lattice constant. We find excellent agreement between experimental data and Monte Carlo simulations of emergent charge-charge interactions.
► Pattern separation is a mechanism for reducing interference among overlapping inputs. ► We examined the role of dentate gyrus in spatial reference memory pattern separation. ► Dentate gyrus lesions ...disrupt place learning for proximal but not distal locations. ► Dentate gyrus supports pattern separation for overlapping spatial reference memories.
The hippocampus (HPP) plays a known role in learning novel spatial information. More specifically, the dentate gyrus (DG) hippocampal subregion is thought to support pattern separation, a mechanism for encoding and separating spatially similar events into distinct representations. Several studies have shown that lesions of the dorsal DG (dDG) in rodents result in inefficient spatial pattern separation for working memory; however, it is unclear whether selective dDG lesions disrupt spatial pattern separation for reference memory. Therefore, the current study investigated the role of the dDG in pattern separation using a spatial reference memory paradigm to determine whether the dDG is necessary for acquiring spatial discriminations for adjacent locations. Male Long-Evans rats were randomly assigned to receive bilateral intracranial infusions of colchicine or saline (control) into the dDG. Following recovery from surgery, each rat was pseudo-randomly assigned to an adjacent arm or separate arm condition and subsequently tested on a place-learning task using an eight-arm radial maze. Rats were trained to discriminate between a rewarded arm and a nonrewarded arm that were either adjacent to one another or separated by a distance of two arm positions. Each rat received 10 trials per day and was tested until the animal reached a criterion of nine correct choices out of 10 consecutive trials across 2 consecutive days of testing. Both groups acquired spatial discriminations for the separate condition at similar rates. However, in the adjacent condition, dDG lesioned animals required significantly more trials to reach the learning criterion than controls. The results suggest that dDG lesions decrease efficiency in pattern separation resulting in impairments in the adjacent condition involving greater overlap among the distal cues. Conversely, in the separate condition, there was less overlap among distal cues during encoding and less need for pattern separation. These findings provide further support for a critical role for the dDG in spatial pattern separation by demonstrating the importance of a processing mechanism that is capable of reducing interference among overlapping spatial inputs across a variety of memory demands.
Rise and Fall of the Beringian Steppe Bison Shapiro, Beth; Drummond, Alexei J.; Rambaut, Andrew ...
Science (American Association for the Advancement of Science),
11/2004, Volume:
306, Issue:
5701
Journal Article
Peer reviewed
Open access
The widespread extinctions of large mammals at the end of the Pleistocene epoch have often been attributed to the depredations of humans; here we present genetic evidence that questions this ...assumption. We used ancient DNA and Bayesian techniques to reconstruct a detailed genetic history of bison throughout the late Pleistocene and Holocene epochs. Our analyses depict a large diverse population living throughout Beringia until around 37,000 years before the present, when the population's genetic diversity began to decline dramatically. The timing of this decline correlates with environmental changes associated with the onset of the last glacial cycle, whereas archaeological evidence does not support the presence of large populations of humans in Eastern Beringia until more than 15,000 years later.
Different clones, protocol conditions, instruments, and scoring/readout methods may pose challenges in introducing different PD-L1 assays for immunotherapy. The diagnostic accuracy of using different ...PD-L1 assays interchangeably for various purposes is unknown. The primary objective of this meta-analysis was to address PD-L1 assay interchangeability based on assay diagnostic accuracy for established clinical uses/purposes. A systematic search of the MEDLINE database using PubMed platform was conducted using "PD-L1" as a search term for 01/01/2015 to 31/08/2018, with limitations "English" and "human". 2,515 abstracts were reviewed to select for original contributions only. 57 studies on comparison of two or more PD-L1 assays were fully reviewed. 22 publications were selected for meta-analysis. Additional data were requested from authors of 20/22 studies in order to enable the meta-analysis. Modified GRADE and QUADAS-2 criteria were used for grading published evidence and designing data abstraction templates for extraction by reviewers. PRISMA was used to guide reporting of systematic review and meta-analysis and STARD 2015 for reporting diagnostic accuracy study. CLSI EP12-A2 was used to guide test comparisons. Data were pooled using random-effects model. The main outcome measure was diagnostic accuracy of various PD-L1 assays. The 22 included studies provided 376 2×2 contingency tables for analyses. Results of our study suggest that, when the testing laboratory is not able to use an Food and Drug Administration-approved companion diagnostic(s) for PD-L1 assessment for its specific clinical purpose(s), it is better to develop a properly validated laboratory developed test for the same purpose(s) as the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic, than to replace the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic with a another PD-L1 Food and Drug Administration-approved companion diagnostic that was developed for a different purpose.
Although individuals with Parkinson's disease (PD) evidence moderate deficits in prospective memory (PM), it is not known whether PM deficits confer an increased risk of poorer everyday functioning. ...In the current study, 33 individuals with PD and 26 demographically similar normal controls (NC) were administered performance-based and self-report measures of PM and everyday functioning, including medication and financial management. As compared to NC, PD participants demonstrated significantly lower scores on performance-based measures of PM and financial capacity, worse performance at a trend level on performance-based medication management and endorsed significantly greater self-reported declines in PM and instrumental activities of daily living (iADLs). In the PD sample, the laboratory measure of PM significantly correlated with performance-based measures of financial capacity and medication management and a self-report measure of medication management. Self-reported PM failures significantly correlated with perceived declines in iADLs, worse medication management, and poorer health-related quality of life. Although future studies are needed to examine the incremental ecological validity of PM in PD, findings from this study extend prior research by providing preliminary evidence that PM impairment may play a significant role in a range of critical everyday functions in PD.
The increasing prevalence of older adults living with HIV has raised growing concerns about a possible rise in the incidence of neurocognitive disorders due to HIV and other age-related factors. In ...typical aging, subjective cognitive impairment (SCI) among individuals with normal neurocognitive functioning may be an early manifestation of an incipient neurocognitive disorder. The current study examined the frequency and correlates of SCI in 188 HIV-infected adults without performance-based neurocognitive deficits or a current psychiatric disorder and 133 HIV seronegative comparison participants. All participants completed the Prospective and Retrospective Memory Questionnaire and Profile of Mood States Confusion/Bewilderment scale. Consistent with the diagnostic criteria proposed by Jessen et al. (Alzheimers Dement 10(6):844–852,
2014
), participants were classified with SCI if their scores on either of the self-reported measures was greater than 1.5 SD above the normative mean. A logistic regression controlling for current mood complaints and lifetime history of substance use disorders revealed that HIV infection increased the odds of SCI (odds ratio= 4.5 1.6, 15.4,
p
= 0.004). Among HIV+ individuals, SCI was associated with lower performance-based learning and delayed memory scores (Cohen’s
d
range 0.41–0.42.) and poorer global everyday functioning (odds ratio= 8.5 2.6, 15.9), but not HIV disease severity (
p
s > 0.10). In a sample of individuals without neurocognitive impairment or elevated mood symptoms, HIV disease was associated with a nearly fivefold increased odds of SCI compared to seronegative individuals, which may indicate an increased risk for developing major neurocognitive disorders as these HIV+ individuals age.
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