Abstract
The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism genetic and genome resource for the laboratory mouse. MGD is the authoritative source for ...biological reference data sets related to mouse genes, gene functions, phenotypes, and mouse models of human disease. MGD is the primary outlet for official gene, allele and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. In this report we describe significant enhancements to MGD, including two new graphical user interfaces: (i) the Multi Genome Viewer for exploring the genomes of multiple mouse strains and (ii) the Phenotype-Gene Expression matrix which was developed in collaboration with the Gene Expression Database (GXD) and allows researchers to compare gene expression and phenotype annotations for mouse genes. Other recent improvements include enhanced efficiency of our literature curation processes and the incorporation of Transcriptional Start Site (TSS) annotations from RIKEN’s FANTOM 5 initiative.
Abstract
Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time ...(aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317–Ser339 that was essential for FXII surface binding and activation, thrombin generation and coagulation. Peptides spanning these 23 residues competed with surface-induced FXII activation. Although FXII mutants lacking residues Gln317–Ser339 were susceptible to activation by plasmin and plasma kallikrein, they were ineffective in supporting arterial and venous thrombus formation in mice. Antibodies raised against the Gln317–Ser339 region induced FXII activation and triggered controllable contact activation in solution leading to thrombin generation by the intrinsic pathway of coagulation. The antibody-activated aPTT allows for standardization of particulate aPTT reagents and for sensitive monitoring of coagulation factors VIII, IX, XI.
This paper finds that the political influence of a local mayor on the appointment of the chief administrative officer (CAO) has a negative influence on the financial outcomes of local governments, as ...evidenced by lower municipal bond ratings. This finding suggests that excessive political authority delegated to mayors may restrict managers from using long-term and apolitical financial strategies. The authors urge local governments to have a mechanism that insulates their CAOs from political pressures to increase government efficiency and decrease the risk of corruption.
The EU has adopted the European Farmland Bird Index (EFBI) as a Structural and Sustainable Development Indicator and a proxy for wider biodiversity health on farmland. Changes in the EFBI over coming ...years are likely to reflect how well agri-environment schemes (AES), funded under Pillar 2 (Axis 2) of the Common Agricultural Policy, have been able to offset the detrimental impacts of past agricultural changes and deliver appropriate hazard prevention or risk mitigation strategies alongside current and future agricultural change. The delivery of a stable or positive trend in the EFBI will depend on the provision of sufficient funding to appropriately designed and implemented AES. We present a trait-based framework which can be used to quantify the detrimental impact of land-use change on farmland bird populations across Europe. We use the framework to show that changes in resource availability within the cropped area of agricultural landscapes have been the key driver of current declines in farmland bird populations. We assess the relative contribution of each Member State to the level of the EFBI and explore the relationship between risk contribution and Axis 2 funding allocation. Our results suggest that agricultural changes in each Member State do not have an equal impact on the EFBI, with land-use and management change in Spain having a particularly large influence on its level, and that funding is poorly targeted with respect to biodiversity conservation needs. We also use the framework to predict the EFBI in 2020 for a number of land-use change scenarios. This approach can be used to guide both the development and implementation of targeted AES and the objective distribution of Pillar 2 funds between and within Member States. We hope that this will contribute to the cost-effective and efficient delivery of Rural Development strategy and biodiversity conservation targets.
Spin-transfer torque random access memory (STT-RAM) is a potentially revolutionary universal memory technology that combines the capacity and cost benefits of DRAM, the fast read and write ...performance of SRAM, the non-volatility of Flash, and essentially unlimited endurance. In order to realize a small cell size, high speed and achieve a fully functional STT-RAM chip, the MgO-barrier magnetic tunnel junctions (MTJ) used as the core storage and readout element must meet a set of performance requirements on switching current density, voltage, magneto-resistance ratio (MR), resistance-area product (RA), thermal stability factor (¿) , switching current distribution, read resistance distribution and reliability. In this paper, we report the progress of our work on device design, material improvement, wafer processing, integration with CMOS, and testing for a demonstration STT-RAM test chip, and projections based on modeling of the future characteristics of STT-RAM.
Physicists have long wondered whether the gravitational interactions between matter and antimatter might be different from those between matter and itself. Although there are many indirect ...indications that no such differences exist and that the weak equivalence principle holds, there have been no direct, free-fall style, experimental tests of gravity on antimatter. Here we describe a novel direct test methodology; we search for a propensity for antihydrogen atoms to fall downward when released from the ALPHA antihydrogen trap. In the absence of systematic errors, we can reject ratios of the gravitational to inertial mass of antihydrogen >75 at a statistical significance level of 5%; worst-case systematic errors increase the minimum rejection ratio to 110. A similar search places somewhat tighter bounds on a negative gravitational mass, that is, on antigravity. This methodology, coupled with ongoing experimental improvements, should allow us to bound the ratio within the more interesting near equivalence regime.
Tests sensitive to presymptomatic changes in Alzheimer's disease could be valuable for clinical trials. Accelerated long-term forgetting—during which memory impairment becomes apparent over longer ...periods than usually assessed, despite normal performance on standard cognitive testing—has been identified in other temporal lobe disorders. We assessed whether accelerated long-term forgetting is a feature of presymptomatic autosomal dominant (familial) Alzheimer's disease, and whether there is an association between accelerated long-term forgetting and early subjective memory changes.
This was a cross-sectional study at the Dementia Research Centre, University College London (London, UK). Participants were recruited from a cohort of autosomal dominant Alzheimer's disease families already involved in research at University College London, and had to have a parent known to be affected by an autosomal dominant Alzheimer's disease mutation, and not report any current symptoms of cognitive decline. Accelerated long-term forgetting of three tasks (list, story, and figure recall) was assessed by comparing 7-day recall with initial learning and 30-min recall. 7-day recognition was also assessed. Subjective memory was assessed using the Everyday Memory Questionnaire. The primary outcome measure for each task was the proportion of material retained at 30 min that was recalled 7 days later (ie, 7-day recall divided by 30-min recall). We used linear regression to compare accelerated long-term forgetting scores between mutation carriers and non-carriers (adjusting for age, IQ, and test set) and, for mutation carriers, to assess whether there was an association between accelerated long-term forgetting and estimated years to symptom onset (EYO). Spearman's correlation was used to examine the association between accelerated long-term forgetting and subjective memory scores.
Between Feb 17, 2015 and March 30, 2016, we recruited 35 people. 21 participants were mutation carriers (mean EYO 7·2 years, SD 4·5). Across the three tasks, we detected no differences between carriers and non-carriers for initial learning or 30-min recall. The proportion of material recalled at 7 days was lower in carriers than non-carriers for list (estimated difference in mean for list recall −30·94 percentage points, 95% CI −45·16 to −16·73; p=0·0002), story (–20·10, −33·28 to −6·91; p=0·0048), and figure (–15·41, −26·88 to −3·93; p=0·012) recall. Accelerated long-term forgetting was greater in carriers nearer to their estimated age at onset (p≤0·01 for all three tests). Mutation carriers' 7-day recognition memory was also lower across all tasks (list mean difference −5·80, 95% CI −9·96 to −2·47; p<0·01, story –6·84, −10·94 to −3·37; p<0·01, and figure –17·61, −27·68 to −7·72; p<0·01 recognition). Subjective memory scores were poorer in asymptomatic carriers compared with non-carriers (adjusted difference in means 7·88, 95% CI 1·36 to 14·41; p=0·016), and we found a correlation between accelerated long-term forgetting and subjective memory in mutation carriers.
Accelerated long-term forgetting is an early presymptomatic feature of autosomal dominant Alzheimer's disease, which appears to pre-date other amnestic deficits and might underpin subjective memory complaints in Alzheimer's disease. Accelerated long-term forgetting testing might be useful in presymptomatic Alzheimer's disease trials.
MRC, NIHR, Alzheimer's Research UK, Dementias Platform UK, Dunhill Medical Trust, ERUK, Great Western Research, Health Foundation, Patrick Berthoud Trust.
Self-motion through an environment involves a composite of signals such as visual and vestibular cues. Building upon previous results showing that visual and vestibular signals combine in a ...statistically optimal fashion, we investigated the relative weights of visual and vestibular cues during self-motion. This experiment was comprised of three experimental conditions: vestibular alone, visual alone (with four different standard heading values), and visual-vestibular combined. In the combined cue condition, inter-sensory conflicts were introduced (Δ = ±6° or ±10°). Participants performed a 2-interval forced choice task in all conditions and were asked to judge in which of the two intervals they moved more to the right. The cue-conflict condition revealed the relative weights associated with each modality. We found that even when there was a relatively large conflict between the visual and vestibular cues, participants exhibited a statistically optimal reduction in variance. On the other hand, we found that the pattern of results in the unimodal conditions did not predict the weights in the combined cue condition. Specifically, visual-vestibular cue combination was not predicted solely by the reliability of each cue, but rather more weight was given to the vestibular cue.
Successful integration of auditory and visual inputs is crucial for both basic perceptual functions and for higher-order processes related to social cognition. Autism spectrum disorders (ASD) are ...characterized by impairments in social cognition and are associated with abnormalities in sensory and perceptual processes. Several groups have reported that individuals with ASD are impaired in their ability to integrate socially relevant audiovisual (AV) information, and it has been suggested that this contributes to the higher-order social and cognitive deficits observed in ASD. However, successful integration of auditory and visual inputs also influences detection and perception of nonsocial stimuli, and integration deficits may impair earlier stages of information processing, with cascading downstream effects. To assess the integrity of basic AV integration, we recorded high-density electrophysiology from a cohort of high-functioning children with ASD (7-16 years) while they performed a simple AV reaction time task. Children with ASD showed considerably less behavioral facilitation to multisensory inputs, deficits that were paralleled by less effective neural integration. Evidence for processing differences relative to typically developing children was seen as early as 100 ms poststimulation, and topographic analysis suggested that children with ASD relied on different cortical networks during this early multisensory processing stage.
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