The ultimate goal of cognitive enhancement as an intervention for age-related cognitive decline is transfer to everyday cognitive functioning. Development of training methods that transfer broadly to ...untrained cognitive tasks (far transfer) requires understanding of the neural bases of training and far transfer effects. We used cognitive training to test the hypothesis that far transfer is associated with altered attentional control demands mediated by the dorsal attention network and trained sensory cortex. In an exploratory study, we randomly assigned 42 healthy older adults to six weeks of training on Brain Fitness (BF—auditory perception), Space Fortress (SF—visuomotor/working memory), or Rise of Nations (RON—strategic reasoning). Before and after training, cognitive performance, diffusion-derived white matter integrity, and functional connectivity of the superior parietal cortex (SPC) were assessed. We found the strongest effects from BF training, which transferred to everyday problem solving and reasoning and selectively changed integrity of occipito-temporal white matter associated with improvement on untrained everyday problem solving. These results show that cognitive gain from auditory perception training depends on heightened white matter integrity in the ventral attention network. In BF and SF (which also transferred positively), a decrease in functional connectivity between SPC and inferior temporal lobe (ITL) was observed compared to RON—which did not transfer to untrained cognitive function. These findings highlight the importance for cognitive training of top–down control of sensory processing by the dorsal attention network. Altered brain connectivity – observed in the two training tasks that showed far transfer effects – may be a marker for training success.
•The ultimate goal of cognitive training in the old is enhanced everyday cognition.•We hypothesized that far transfer depends on altered attentional control.•A randomized trial compared 3 training tasks on transfer and brain change in aging.•Everyday cognition improved from auditory perception and skill acquisition training.•Connectivity changed in ventral and dorsal attention networks for these 2 tasks.
Hepatitis C virus (HCV) cannot be grown in vitro, making biochemical identification of new drug targets especially important. HCV p7 is a small hydrophobic protein of unknown function, yet necessary ...for particle infectivity in related viruses Harada, T. et al., (2000) J. Virol. 74, 9498–9506. We show that p7 can be cross-linked in vivo as hexamers. Escherichia coli expressed p7 fusion proteins also form hexamers in vitro. These and HIS-tagged p7 function as calcium ion channels in black lipid membranes. This activity is abrogated by Amantadine, a compound that inhibits ion channels of influenza Hay, A.J. et al. (1985) EMBO J. 4, 3021–3024; Duff, K.C. and Ashley, R.H. (1992) Virology 190, 485–489 and has recently been shown to be active in combination with current HCV therapies.
Chemotherapy for patients chronically infected with hepatitis C virus (HCV) is ineffective in over 50% of cases, generating a high demand for new drug targets. The p7 protein of HCV displays membrane ...channel activity
in vitro and is essential for replication
in vivo though its precise role in the virus life cycle is unknown
. p7 channel activity can be specifically inhibited by several classes of compounds, making this protein an attractive candidate for drug development, though techniques used to date in characterising this protein are unsuited to compound library screening. Here we describe an assay for the channel forming ability of p7 based on the release of a fluorescent indicator from liposomes. We show that recombinant p7 from genotype 1b HCV causes a dose-dependent release of dye when mixed with liposomes and that this property is enhanced at acidic pH. We demonstrate that this activity is due to the formation of a size-selective pore rather than non-specific disruption of liposomes and that activity can be blocked by amantadine and several other compounds, validating it as a measure of p7 channel function. This system provides the first convenient
in vitro assay for exploiting p7 as a therapeutic target.
We previously identified the function of the hepatitis C virus (HCV) p7 protein as an ion channel in artificial lipid bilayers and demonstrated that this in vitro activity is inhibited by amantadine. ...Here we show that the ion channel activity of HCV p7 expressed in mammalian cells can substitute for that of influenza virus M2 in a cell-based assay. This was also the case for the p7 from the related virus, bovine viral diarrhoea virus (BVDV). Moreover, amantadine was shown to abrogate HCV p7 function in this assay at a concentration that specifically inhibits M2. Mutation of a conserved basic loop located between the two predicted trans-membrane alpha helices rendered HCV p7 non-functional as an ion channel. The intracellular localization of p7 was unaffected by this mutation and was found to overlap significantly with membranes associated with mitochondria. Demonstration of p7 ion channel activity in cellular membranes and its inhibition by amantadine affirm the protein as a target for future anti-viral chemotherapy.
This report had its beginnings at the Third International Symposium on Toroidal Plasma Confinement held in Garching/Munich, Federal Republic of Germany, March 26–30, 1973. The American scientists who ...attended this conference agreed to assist in preparing a summary of the status of the field. Since that time, the authors of this report have had the opportunity to incorporate progress reported at the VI European Conference on Plasma Physics and Controlled Fusion, held in Moscow, U.S.S.R., from July 29 to August 3, 1973. The report has been available previously only as U.S. Atomic Energy Commission Report WASH-1295 (1974). It was the first comprehensive survey of the status of the tokamak fusion research concept, which was to become the cornerstone of the world fusion effort for the next quarter century. It provided the basis for the rapid buildup of the U.S. tokamak program during the latter half of the 1970's and is published now to archive its historical significance.
The impact of maritime transport in the financial improvement of any nation cannot be over-accentuated. In the meantime, the result of the maritime exercises on the earth has been a worry and the ...subsequent impact on the economy. Nigeria is a developing country and could too have a portrayal as an import-oriented country; hence, it depends vigorously on sea transport for the importation of products. This study targets analyzing the connection between marine pollution, maritime transport, and financial development in Nigeria. Time arrangement information that spread over from the year 2000 to 2018 was used, and Autoregressive Distributive Lag (ARDL) model was utilized for the investigation. The discoveries from this examination uncover a long-run relationship running from marine pollution to economic growth. It was additionally found from this examination that a critical short-run relationship exists between maritime transportation and environmental pollution. Additionally, huge long-run causal effect of sea transport was found in the financial development of Nigeria. Further investigation from the examination demonstrates a long-run unidirectional connection between environmental pollution and financial development; and exchange and economic growth, while the bi-directional causal relationship won between maritime transport and economic growth. The investigation, in this manner, proposes that Nigeria ought to improve both environmentally and economically as a result of its negative job in ecological quality is more overwhelming than its advantages in monetary development.
Beginning in 1983, a sharp increase was noted in the number of new admissions for cocaine abuse to the only psychiatric hospital and to the primary outpatient psychiatric clinic in the Bahamas. For ...the two facilities combined, new admissions for cocaine abuse increased from none in 1982 to 69 in 1983 and to 523 in 1984. Although there was some evidence for a rise in cocaine use during this time, as the drug became cheaper and more available, a primary cause of this medical epidemic seemed to be a switch by pushers from selling cocaine hydrochloride, which has a low addictive potential, to almost exclusive selling of cocaine free base, which has a very high addictive potential and causes medical and psychological problems. Although the use of free cocaine base is rising around the world, this is the first report of a nationwide medical epidemic due almost exclusively to this form of the drug, although similar problems are reported with smoking coca paste in South America.
PDF
