Working memory training does not enhance older adults' cognitive skills: A comprehensive meta-analysis

© 2019 The Authors In the last two decades, considerable efforts have been devoted to finding a way to enhance cognitive function by cognitive training. To date, the attempt to boost broad cognitive functions in the general population has failed. However, it is still possible that some cognitive training regimens exert a positive influence on specific populations, such as older adults. In this meta-analytic review, we investigated the effects of working memory (WM) training on older adults' cognitive skills. Three robust-variance-estimation meta-analyses (N = 2140, m = 43, and k = 698) were run to analyze the effects of the intervention on (a) the trained tasks, (b) near-transfer measures, and (c) far-transfer measures. While large effects were found for the trained tasks (g¯ = 0.877), only modest (g¯ = 0.274) and near-zero (g¯ = 0.121) effects were obtained in the near-transfer and far-transfer meta-analyses, respectively. Publication-bias analysis provided adjusted estimates that were slightly lower. Moreover, when active control groups were implemented, the far-transfer effects were null (g¯ = −0.008). Finally, the effects were highly consistent across studies (i.e., low or null true heterogeneity), especially in the near- and far-transfer models. While confirming the difficulty in obtaining transfer effects with cognitive training, these results corroborate recent empirical evidence suggesting that WM is not isomorphic with other fundamental cognitive skills such as fluid intelligence

Anisotropic Magnetoresistance Effects in Fe, Co, Ni, Fe_4N, and Half-Metallic Ferromagnet: A Systematic Analysis

We theoretically analyze the anisotropic magnetoresistance (AMR) effects of bcc Fe (+), fcc Co (+), fcc Ni (+), Fe$_4$N (-), and a half-metallic ferromagnet (-). The sign in each ( ) represents the sign of the AMR ratio observed experimentally. We here use the two-current model for a system consisting of a spin-polarized conduction state and localized d states with spin--orbit interaction. From the model, we first derive a general expression of the AMR ratio. The expression consists of a resistivity of the conduction state of the $\sigma$ spin ($\sigma=\uparrow$ or $\downarrow$), $\rho_{s \sigma}$, and resistivities due to s--d scattering processes from the conduction state to the localized d states. On the basis of this expression, we next find a relation between the sign of the AMR ratio and the s--d scattering process. In addition, we obtain expressions of the AMR ratios appropriate to the respective materials. Using the expressions, we evaluate their AMR ratios, where the expressions take into account the values of $\rho_{s \downarrow}/\rho_{s \uparrow}$ of the respective materials. The evaluated AMR ratios correspond well to the experimental results.Comment: 17 pages, 12 figures, to be published in J. Phys. Soc. Jpn, minor mistakes corrected, final versio

Systematic generation of in vivo G protein-coupled receptor mutants in the rat

G-protein-coupled receptors (GPCRs) constitute a large family of cell surface receptors that are involved in a wide range of physiological and pathological processes, and are targets for many therapeutic interventions. However, genetic models in the rat, one of the most widely used model organisms in physiological and pharmacological research, are largely lacking. Here, we applied N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis to generate an in vivo GPCR mutant collection in the rat. A pre-selected panel of 250 human GPCR homologs was screened for mutations in 813 rats, resulting in the identification of 131 non-synonymous mutations. From these, seven novel potential rat gene knockouts were established as well as 45 lines carrying missense mutations in various genes associated with or involved in human diseases. We provide extensive in silico modeling results of the missense mutations and show experimental data, suggesting loss-of-function phenotypes for several models, including Mc4r and Lpar1. Taken together, the approach used resulted not only in a set of novel gene knockouts, but also in allelic series of more subtle amino acid variants, similar as commonly observed in human disease. The mutants presented here may greatly benefit studies to understand specific GPCR function and support the development of novel therapeutic strategies

Reptiles and Mammals Have Differentially Retained Long Conserved Noncoding Sequences from the Amniote Ancestor

Many noncoding regions of genomes appear to be essential to genome function. Conservation of large numbers of noncoding sequences has been reported repeatedly among mammals but not thus far among birds and reptiles. By searching genomes of chicken (Gallus gallus), zebra finch (Taeniopygia guttata), and green anole (Anolis carolinensis), we quantified the conservation among birds and reptiles and across amniotes of long, conserved noncoding sequences (LCNS), which we define as sequences ≥500 bp in length and exhibiting ≥95% similarity between species. We found 4,294 LCNS shared between chicken and zebra finch and 574 LCNS shared by the two birds and Anolis. The percent of genomes comprised by LCNS in the two birds (0.0024%) is notably higher than the percent in mammals (<0.0003% to <0.001%), differences that we show may be explained in part by differences in genome-wide substitution rates. We reconstruct a large number of LCNS for the amniote ancestor (ca. 8,630) and hypothesize differential loss and substantial turnover of these sites in descendent lineages. By contrast, we estimated a small role for recruitment of LCNS via acquisition of novel functions over time. Across amniotes, LCNS are significantly enriched with transcription factor binding sites for many developmental genes, and 2.9% of LCNS shared between the two birds show evidence of expression in brain expressed sequence tag databases. These results show that the rate of retention of LCNS from the amniote ancestor differs between mammals and Reptilia (including birds) and that this may reflect differing roles and constraints in gene regulation