What you know can influence what you are going to know (especially for older adults)

Stimuli related to an individual's knowledge/experience are often more memorable than abstract stimuli, particularly for older adults. This has been found when material that is congruent with knowledge is contrasted with material that is incongruent with knowledge, but there is little research on a possible graded effect of congruency. The present study manipulated the degree of congruency of study material with participants’ knowledge. Young and older participants associated two famous names to nonfamous faces, where the similarity between the nonfamous faces and the real famous individuals varied. These associations were incrementally easier to remember as the name-face combinations became more congruent with prior knowledge, demonstrating a graded congruency effect, as opposed to an effect based simply on the presence or absence of associations to prior knowledge. Older adults tended to show greater susceptibility to the effect than young adults, with a significant age difference for extreme stimuli, in line with previous literature showing that schematic support in memory tasks particularly benefits older adults

Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

A structurally derived model of subunit‐dependent NMDA receptor function

NMDA receptors (NMDARs) are tetrameric complexes comprising two glycine‐binding GluN1 and two glutamate‐binding GluN2 subunits. Four GluN2 subunits encoded by different genes can produce up to 10 different di‐ and triheteromeric receptors. In addition, some neurological patients contain a de novo mutation or inherited rare variant in only one subunit. There is currently no mechanistic framework to describe tetrameric receptor function that can be extended to receptors with two different GluN1 or GluN2 subunits. Here we use the structural features of glutamate receptors to develop a mechanism describing both single channel and macroscopic NMDAR currents. We propose that each agonist‐bound subunit undergoes some rate‐limiting conformational change after agonist binding, prior to channel opening. We hypothesize that this conformational change occurs within a triad of interactions between a short helix preceding the M1 transmembrane helix, the highly conserved M3 motif encoded by the residues SYTANLAAF, and the linker preceding the M4 transmembrane helix of the adjacent subunit. Molecular dynamics simulations suggest that pre‐M1 helix motion is uncorrelated between subunits, which we interpret to suggest independent subunit‐specific conformational changes may influence these pre‐gating steps. According to this interpretation, these conformational changes are the main determinants of the key kinetic properties of NMDA receptor activation following agonist binding, and so these steps sculpt their physiological role. We show that this structurally derived tetrameric model describes both single channel and macroscopic data, giving a new approach to interpreting functional properties of synaptic NMDARs that provides a logical framework to understanding receptors with non‐identical subunits

Assessing the psychometric and ecometric properties of neighborhood scales using adolescent survey data from urban and rural Scotland

This work was supported by NHS Health Scotland and the University of St Andrews.Background:  Despite the well-established need for specific measurement instruments to examine the relationship between neighborhood conditions and adolescent well-being outcomes, few studies have developed scales to measure features of the neighborhoods in which adolescents reside. Moreover, measures of neighborhood features may be operationalised differently by adolescents living in different levels of urban/rurality. This has not been addressed in previous studies. The objectives of this study were to: 1) establish instruments to measure adolescent neighborhood features at both the individual and neighborhood level, 2) assess their psychometric and ecometric properties, 3) test for invariance by urban/rurality, and 4) generate neighborhood level scores for use in further analysis. Methods:  Data were from the Scottish 2010 Health Behaviour in School-aged Children Survey, which included an over-sample of rural adolescents. The survey responses of interest came from questions designed to capture different facets of the local area in which each respondent resided. Intermediate data zones were used as proxies for neighborhoods. Internal consistency was evaluated by Cronbach’s alpha. Invariance was examined using confirmatory factor analysis. Multilevel models were used to estimate ecometric properties and generate neighborhood scores. Results:  Two constructs labeled neighborhood social cohesion and neighborhood disorder were identified. Adjustment was made to the originally specified model to improve model fit and measures of invariance. At the individual level, reliability was .760 for social cohesion and .765 for disorder, and between .524 and .571 for both constructs at the neighborhood level. Individuals in rural areas experienced greater neighborhood social cohesion and lower levels of neighborhood disorder compared with those in urban areas. Conclusions:  The scales are appropriate for measuring neighborhood characteristics experienced by adolescents across urban and rural Scotland, and can be used in future studies of neighborhoods and health. However, trade-offs between neighborhood sample size and reliability must be considered.Publisher PDFPeer reviewe

The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

Analysis of a viral metagenomic library from 200 m depth in Monterey Bay, California constructed by direct shotgun cloning

<p>Abstract</p> <p>Background</p> <p>Viruses have a profound influence on both the ecology and evolution of marine plankton, but the genetic diversity of viral assemblages, particularly those in deeper ocean waters, remains poorly described. Here we report on the construction and analysis of a viral metagenome prepared from below the euphotic zone in a temperate, eutrophic bay of coastal California.</p> <p>Methods</p> <p>We purified viruses from approximately one cubic meter of seawater collected from 200m depth in Monterey Bay, CA. DNA was extracted from the virus fraction, sheared, and cloned with no prior amplification into a plasmid vector and propagated in <it>E. coli </it>to produce the MBv200m library. Random clones were sequenced by the Sanger method. Sequences were assembled then compared to sequences in GenBank and to other viral metagenomic libraries using BLAST analyses.</p> <p>Results</p> <p>Only 26% of the 881 sequences remaining after assembly had significant (E ≤ 0.001) BLAST hits to sequences in the GenBank nr database, with most being matches to bacteria (15%) and viruses (8%). When BLAST analysis included environmental sequences, 74% of sequences in the MBv200m library had a significant match. Most of these hits (70%) were to microbial metagenome sequences and only 0.7% were to sequences from viral metagenomes. Of the 121 sequences with a significant hit to a known virus, 94% matched bacteriophages (Families <it>Podo</it>-, <it>Sipho</it>-, and <it>Myoviridae</it>) and 6% matched viruses of eukaryotes in the Family <it>Phycodnaviridae </it>(5 sequences) or the Mimivirus (2 sequences). The largest percentages of hits to viral genes of known function were to those involved in DNA modification (25%) or structural genes (17%). Based on reciprocal BLAST analyses, the MBv200m library appeared to be most similar to viral metagenomes from two other bays and least similar to a viral metagenome from the Arctic Ocean.</p> <p>Conclusions</p> <p>Direct cloning of DNA from diverse marine viruses was feasible and resulted in a distribution of virus types and functional genes at depth that differed in detail, but were broadly similar to those found in surface marine waters. Targeted viral analyses are useful for identifying those components of the greater marine metagenome that circulate in the subcellular size fraction.</p

Electrophysiological Correlates of Strategic Monitoring in Event-Based and Time-Based Prospective Memory

Prospective memory (PM) is the ability to remember to accomplish an action when a particular event occurs (i.e., event-based PM), or at a specific time (i.e., time-based PM) while performing an ongoing activity. Strategic Monitoring is one of the basic cognitive functions supporting PM tasks, and involves two mechanisms: a retrieval mode, which consists of maintaining active the intention in memory; and target checking, engaged for verifying the presence of the PM cue in the environment. The present study is aimed at providing the first evidence of event-related potentials (ERPs) associated with time-based PM, and at examining differences and commonalities in the ERPs related to Strategic Monitoring mechanisms between event- and time-based PM tasks