Boosting Long-term Memory via Wakeful Rest: Intentional Rehearsal is not Necessary, Automatic Consolidation is Sufficient.

<div><p>People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is <i>not</i> dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is <i>sufficient</i> for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.</p></div

From evidence to best practice in the management of fractures of the distal radius in adults: working towards a research agenda

BACKGROUND: Fracture of the distal radius is a common clinical problem, particularly in older white women with osteoporosis. We report our work towards evidence-based and patient-centred care for adults with these injuries. METHODS: We developed a systematic programme of research that built on our systematic review of the evidence of effectiveness of treatment interventions for these fractures. We devised schemata showing 'typical' care pathways and identified over 100 patient management questions. These depicted the more important decisions taken when progressing along each care pathway. We compiled a comprehensive document summarising the evidence available for each decision point from our reviews of randomised trials of treatment interventions. Using these documents, we undertook a formal and structured consultation process involving key players, including a patient representative, to obtain their views on the available evidence and to establish a research agenda. The resulting feedback was then processed and interpreted, using systematic methods. RESULTS: Some evidence from 114 randomised trials was available for 31 of the 117 patient management questions. However, there was sufficient evidence to base some conclusions of effectiveness for particular interventions in only five of these. Though only 60% of those approached responded, the responses received from the consultation group were often comprehensive and provided important insights into treatment practice and policy. There was a clear acceptance of the aims of the project and, aside from some suggestions for the more explicit inclusion of secondary prevention and management of complications, of the care pathways scheme. Though some respondents stressed that randomised trials were not always appropriate, there was no direct overall criticism of the evidence document and underlying processes. We were able to identify important core themes that underpin management decisions and research from the feedback of the consultation exercise. CONCLUSIONS: Overall, this project is an important advance towards evidence-based and patient-centred management of adults with distal radial fractures. It exposes the serious deficiency in the available evidence but also provides a template for further action. As well as being a valuable basis for viewing and informing current practice, the insights gained from this project should inform a future research agenda

Removal of Heterologous Sequences from Plasmodium falciparum Mutants Using FLPe-Recombinase

Genetically-modified mutants are now indispensable Plasmodium gene-function reagents, which are also being pursued as genetically attenuated parasite vaccines. Currently, the generation of transgenic malaria-parasites requires the use of drug-resistance markers. Here we present the development of an FRT/FLP-recombinase system that enables the generation of transgenic parasites free of resistance genes. We demonstrate in the human malaria parasite, P. falciparum, the complete and efficient removal of the introduced resistance gene. We targeted two neighbouring genes, p52 and p36, using a construct that has a selectable marker cassette flanked by FRT-sequences. This permitted the subsequent removal of the selectable marker cassette by transient transfection of a plasmid that expressed a 37°C thermostable and enhanced FLP-recombinase. This method of removing heterologous DNA sequences from the genome opens up new possibilities in Plasmodium research to sequentially target multiple genes and for using genetically-modified parasites as live, attenuated malaria vaccines

Complementarity of Spike- and Rate-Based Dynamics of Neural Systems

Relationships between spiking-neuron and rate-based approaches to the dynamics of neural assemblies are explored by analyzing a model system that can be treated by both methods, with the rate-based method further averaged over multiple neurons to give a neural-field approach. The system consists of a chain of neurons, each with simple spiking dynamics that has a known rate-based equivalent. The neurons are linked by propagating activity that is described in terms of a spatial interaction strength with temporal delays that reflect distances between neurons; feedback via a separate delay loop is also included because such loops also exist in real brains. These interactions are described using a spatiotemporal coupling function that can carry either spikes or rates to provide coupling between neurons. Numerical simulation of corresponding spike- and rate-based methods with these compatible couplings then allows direct comparison between the dynamics arising from these approaches. The rate-based dynamics can reproduce two different forms of oscillation that are present in the spike-based model: spiking rates of individual neurons and network-induced modulations of spiking rate that occur if network interactions are sufficiently strong. Depending on conditions either mode of oscillation can dominate the spike-based dynamics and in some situations, particularly when the ratio of the frequencies of these two modes is integer or half-integer, the two can both be present and interact with each other

A Secure Semi-Field System for the Study of Aedes aegypti

Novel vector control strategies require validation in the field before they can be widely accepted. Semi-field system (SFS) containment facilities are an intermediate step between laboratory and field trials that offer a safe, controlled environment that replicates field conditions. We developed a SFS laboratory and cage complex that simulates an urban house and yard, which is the primary habitat for Aedes aegypti, the mosquito vector of dengue in Cairns Australia. The SFS consists of a Quarantine Insectary Level-2 (QIC-2) laboratory, containing 3 constant temperature rooms, that is connected to two QIS-2 cages for housing released mosquitoes. Each cage contains the understory of a “Queenslander” timber house and associated yard. An automated air conditioning system keeps temperature and humidity to within 1°C and 5% RH of ambient conditions, respectively. Survival of released A. aegypti was high, especially for females. We are currently using the SFS to investigate the invasion of strains of Wolbachia within populations of A. aegypti

Allele Intersection Analysis: A Novel Tool for Multi Locus Sequence Assignment in Multiply Infected Hosts

Wolbachia are wide-spread, endogenous α-Proteobacteria of arthropods and filarial nematodes. 15–75% of all insect species are infected with these endosymbionts that alter their host's reproduction to facilitate their spread. In recent years, many insect species infected with multiple Wolbachia strains have been identified. As the endosymbionts are not cultivable outside living cells, strain typing relies on molecular methods. A Multi Locus Sequence Typing (MLST) system was established for standardizing Wolbachia strain identification. However, MLST requires hosts to harbour individual and not multiple strains of supergroups without recombination. This study revisits the applicability of the current MLST protocols and introduces Allele Intersection Analysis (AIA) as a novel approach. AIA utilizes natural variations in infection patterns and allows correct strain assignment of MLST alleles in multiply infected host species without the need of artificial strain segregation. AIA identifies pairs of multiply infected individuals that share Wolbachia and differ in only one strain. In such pairs, the shared MLST sequences can be used to assign alleles to distinct strains. Furthermore, AIA is a powerful tool to detect recombination events. The underlying principle of AIA may easily be adopted for MLST approaches in other uncultivable bacterial genera that occur as multiple strain infections and the concept may find application in metagenomic high-throughput parallel sequencing projects

Selective modulation of subtype III IP3R by Akt regulates ER Ca2+ release and apoptosis

Ca2+ transfer from endoplasmic reticulum (ER) to mitochondria can trigger apoptotic pathways by inducing release of mitochondrial pro-apoptotic factors. Three different types of inositol 1,4,5-trisphosphate receptor (IP3R) serve to discharge Ca2+ from ER, but possess some peculiarities, especially in apoptosis induction. The anti-apoptotic protein Akt can phosphorylate all IP3R isoforms and protect cells from apoptosis, reducing ER Ca2+ release. However, it has not been elucidated which IP3R subtypes mediate these effects. Here, we show that Akt activation in COS7 cells, which lack of IP3R I, strongly suppresses IP3-mediated Ca2+ release and apoptosis. Conversely, in SH-SY 5Y cells, which are type III-deficient, Akt is unable to modulate ER Ca2+ flux, losing its anti-apoptotic activity. In SH-SY 5Y-expressing subtype III, Akt recovers its protective function on cell death, by reduction of Ca2+ release. Moreover, regulating Ca2+ flux to mitochondria, Akt maintains the mitochondrial integrity and delays the trigger of apoptosis, in a type III-dependent mechanism. These results demonstrate a specific activity of Akt on IP3R III, leading to diminished Ca2+ transfer to mitochondria and protection from apoptosis, suggesting an additional level of cell death regulation mediated by Akt

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente