Exogenous spatial precuing reliably modulates object processing but not object substitution masking

Object substitution masking (OSM) is used in behavioral and imaging studies to investigate processes associated with the formation of a conscious percept. Reportedly, OSM occurs only when visual attention is diffusely spread over a search display or focused away from the target location. Indeed, the presumed role of spatial attention is central to theoretical accounts of OSM and of visual processing more generally (Di Lollo, Enns, & Rensink, Journal of Experimental Psychology: General 129:481–507, 2000). We report a series of five experiments in which valid spatial precuing is shown to enhance the ability of participants to accurately report a target but, in most cases, without affecting OSM. In only one experiment (Experiment 5) was a significant effect of precuing observed on masking. This is in contrast to the reliable effect shown across all five experiments in which precuing improved overall performance. The results are convergent with recent findings from Argyropoulos, Gellatly, and Pilling (Journal of Experimental Psychology: Human Perception and Performance 39:646–661, 2013), which show that OSM is independent of the number of distractor items in a display. Our results demonstrate that OSM can operate independently of focal attention. Previous claims of the strong interrelationship between OSM and spatial attention are likely to have arisen from ceiling or floor artifacts that restricted measurable performance

Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii

Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth. Phenotypic analysis revealed that all three CaMs contribute to parasite motility, invasion, and egress from host cells, and that they act downstream of microneme and rhoptry secretion. Super-resolution microscopy localized all three CaMs to the conoid where they overlap with myosin H (MyoH), a motor protein that is required for invasion. Biotinylation using BirA fusions with the CaMs labeled a number of apical proteins including MyoH and its light chain MLC7, suggesting they may interact. Consistent with this hypothesis, disruption of MyoH led to degradation of CaM3, or redistribution of CaM1 and CaM2. Collectively, our findings suggest these CaMs may interact with MyoH to control motility and cell invasion

A Small-Molecule Inhibitor of T. gondii Motility Induces the Posttranslational Modification of Myosin Light Chain-1 and Inhibits Myosin Motor Activity

Toxoplasma gondii is an obligate intracellular parasite that enters cells by a process of active penetration. Host cell penetration and parasite motility are driven by a myosin motor complex consisting of four known proteins: TgMyoA, an unconventional Class XIV myosin; TgMLC1, a myosin light chain; and two membrane-associated proteins, TgGAP45 and TgGAP50. Little is known about how the activity of the myosin motor complex is regulated. Here, we show that treatment of parasites with a recently identified small-molecule inhibitor of invasion and motility results in a rapid and irreversible change in the electrophoretic mobility of TgMLC1. While the precise nature of the TgMLC1 modification has not yet been established, it was mapped to the peptide Val46-Arg59. To determine if the TgMLC1 modification is responsible for the motility defect observed in parasites after compound treatment, the activity of myosin motor complexes from control and compound-treated parasites was compared in an in vitro motility assay. TgMyoA motor complexes containing the modified TgMLC1 showed significantly decreased motor activity compared to control complexes. This change in motor activity likely accounts for the motility defects seen in the parasites after compound treatment and provides the first evidence, in any species, that the mechanical activity of Class XIV myosins can be modulated by posttranslational modifications to their associated light chains

Primate evolution: Evidence from the fossil record, comparative morphology, and molecular biology

Our understanding of primate evolution is ultimately based on patterns of phyletic relationship and morphological change documented in the fossil record. Stratophenetic interpretation of living and fossil primates yields an objective alternative to the arbitrary scala naturae assumed implicitly in traditional comparative biology. Fossils provide an outline of primate history constraining comparative analyses incorporating taxa and morphological characteristics not represented in the fossil record. Extant taxa without known prehistoric relatives may be interpolated into this outline using deductive cladistic analysis of morphological characteristics and overall molecular similarity. Cladistic analysis provides a method for evaluating the relative strength of stratophenetic links between taxa. The phyletic node connecting Anthropoidea-Adapoidea-Lemuroidea is analyzed here as an example: the link between Eocene Adapoidea and primitive Anthropoidea appears stronger than that between Adapoidea and Lemuroidea because it is based on shared-derived rather than shared-primitive characteristics. Full integration of molecular results with morphological information requires a better understanding of rates of molecular change over geological time. Rates of molecular evolution can be studied using paleontologically documented divergence times for Prosimii-Anthropoidea (ca. 55 m.y.B.P.), Platyrrhini-Catarrhini (ca. 40 m.y.B.P.), and Hominoidea-Cercopithecoidea (ca. 25 m.y.B.P.). Immunological distances combined with these divergence times indicate that primate albumin, widely used as a molecular clock in primatology, has evolved nonlinearly over geological time. A nonlinear albumin clock yields divergence times of about 9 million years before present for humans and chimpanzees, and about 13 million years before present for humans and orangutans (compared with 4 m.y.B.P. and 7 m.y.B.P., respectively, based on a linear albumin clock). Apparent slowing of albumin evolution over time remains to be fully explained. Other proteins and nucleic acids may provide better clocks. Cladistic analysis of morphological characteristics and comparative study of molecular structure, interpreted in the context of the fossil record, promise to contribute to a more complete understanding of primate evolution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37624/1/1330270504_ftp.pd

Evaluation of an online Diabetes Needs Assessment Tool (DNAT) for health professionals: a randomised controlled trial

Background: Continuous medical education is traditionally reliant to a large extent on self-directed learning based on individuals' perceived learning priorities. Evidence suggests that this ability to self-assess is limited, and more so in the least competent. Therefore, it may be of benefit to utilise some form of external assessment for this purpose. Many diabetes educational programmes have been introduced, but few have been assessed for their benefit in a systematic manner. As diabetes is an increasingly prevalent disease, methods for the dissemination and understanding of clinical guidelines need to be explored for their effectiveness. This paper describes the study design of a randomised controlled trial to evaluate the effectiveness of using an interactive online Diabetes Needs Assessment Tool (DNAT), that builds a learning curriculum based on identified knowledge gaps, compared with conventional self-directed learning. The study assesses the effect of these interventions on health professionals' knowledge of diabetes management, evaluates the acceptability of this process of learning and self-reported changes in clinical practice as a result of this novel educational process. Methods: Following a baseline assessment, participants will be randomised to undergo a 4-month learning period where they will either be given access to the diabetes learning modules alone (control group) or a Diabetes Needs Assessment Tool (DNAT) plus the diabetes learning modules (intervention group). On completion of the DNAT, a personalised learning report will be created for each participant identifying needs alongside individualised recommendations of the most appropriate learning modules to meet those requirements. All participants will complete a Diabetes Knowledge Test before and immediately after the allocated learning and the primary outcome will be the state of knowledge at 4 months. Learners will also be surveyed immediately after the learning period to assess the acceptability of the learning formats and the perceived usefulness and usability of the materials. After a further month, all learners will receive a series of questions to evaluate self-reported changes in clinical practice as a result of this educational experience and asked to include specific examples of any changes in their diabetes care practice

Progression to microalbuminuria in patients with type 1 diabetes: a seven-year prospective study

<p>Abstract</p> <p>Background</p> <p>The presence of microalbuminuria can be associated with overt nephropathy and cardiovascular disease in patients with type 1 diabetes (T1D). We aimed to determine the incidence and evaluate the baseline predictors for the development of microalbuminuria in patients with T1D.</p> <p>Methods</p> <p>This study is a longitudinal cohort study of 122 normoalbuminuric patients with T1D who were receiving routine clinical care at baseline. A detailed medical history was taken, and a physical examination was performed at baseline. All of the patients were regularly examined for diabetes-associated complications. An analysis of predictors was performed using the Cox regression.</p> <p>Results</p> <p>Over 6.81 (3.59-9.75) years of follow-up, 50 (41%) of the patients developed microalbuminuria. The incidence density was 6.79/100 people per year (95% CI 5.04-8.95), and the microalbuminuria developed after 5.9 (2.44-7.76) and 11 (5-15) years of follow-up and diabetes duration, respectively. After an individual Cox regression, the baseline variables associated with the development of microalbuminuria were age, age at diagnosis, duration of diabetes, systolic and diastolic blood pressure, fasting glycemia, body mass index (BMI), total cholesterol and triglycerides levels, cholesterol/HDL ratio and a family history of type 2 diabetes.After a multivariate Cox regression, the only independent factors associated with the development of microalbuminuria were BMI [HR 1.12 (1.03-1.21)] and cholesterol/HDL ratio [HR 1.32 (1.05-1.67)].</p> <p>Conclusions</p> <p>A higher BMI and cholesterol/HDL ratio increased the risk of developing microalbuminuria in young patients with T1D after a short follow-up. Both risk factors are modifiable and should be identified early and followed closely.</p

Altered postural sway in patients suffering from non-specific neck pain and whiplash associated disorder - A systematic review of the literature

To assess differences in center of pressure (COP) measures in patients suffering from non-specific neck pain (NSNP) or whiplash-associated disorder (WAD) compared to healthy controls and any relationship between changes in postural sway and the presence of pain, its intensity, previous pain duration and the perceived level of disability. Summary of Background data: Over the past 20 years, the center of pressure (COP) has been commonly used as an index of postural stability in standing. While several studies investigated COP excursions in neck pain and WAD patients and compared these to healthy individuals, no comprehensive analysis of the reported differences in postural sway pattern exists. Search methods: Six online databases were systematically searched followed by a manual search of the retrieved papers. Selection Criteria: Papers comparing COP measures derived from bipedal static task conditions on a force plate of non-specific neck pain and WAD sufferers to those of healthy controls. Data collection and analysis: Two reviewers independently screened titles and abstracts for relevance. Screening for final inclusion, data extraction and quality assessment were carried out with a third reviewer to reconcile differences

Evaluation of an online interactive Diabetes Needs Assessment Tool (DNAT) versus online self-directed learning: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Methods for the dissemination, understanding and implementation of clinical guidelines need to be examined for their effectiveness to help doctors integrate guidelines into practice. The objective of this randomised controlled trial was to evaluate the effectiveness of an interactive online Diabetes Needs Assessment Tool (DNAT) (which constructs an e-learning curriculum based on individually identified knowledge gaps), compared with self-directed e-learning of diabetes guidelines.</p> <p>Methods</p> <p>Health professionals were randomised to a 4-month learning period and either given access to diabetes learning modules alone (control group) or DNAT plus learning modules (intervention group). Participants completed knowledge tests before and after learning (primary outcome), and surveys to assess the acceptability of the learning and changes to clinical practice (secondary outcomes).</p> <p>Results</p> <p>Sixty four percent (677/1054) of participants completed both knowledge tests. The proportion of nurses (5.4%) was too small for meaningful analysis so they were excluded. For the 650 doctors completing both tests, mean (SD) knowledge scores increased from 47.4% (12.6) to 66.8% (11.5) [intervention group (n = 321, 64%)] and 47.3% (12.9) to 67.8% (10.8) [control group (n = 329, 66%)], (ANCOVA p = 0.186). Both groups were satisfied with the usability and usefulness of the learning materials. Seventy seven percent (218/284) of the intervention group reported combining the DNAT with the recommended reading materials was "<it>very useful"/"useful"</it>. The majority in both groups (184/287, 64.1% intervention group and 206/299, 68.9% control group) [95% CI for the difference (-2.8 to 12.4)] reported integrating the learning into their clinical practice.</p> <p>Conclusions</p> <p>Both groups experienced a similar and significant improvement in knowledge. The learning materials were acceptable and participants incorporated the acquired knowledge into practice.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN67215088">ISRCTN67215088</a></p

Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging

This study investigates the temporal and spatial interchange of the aromatic amino acid phenylalanine (Phe) between human retinal pigment epithelial cell line (ARPE-19) and tachyzoites of the apicomplexan protozoan parasite Toxoplasma gondii (T. gondii). Stable isotope labelling by amino acids in cell culture (SILAC) is combined with Raman micro-spectroscopy to selectively monitor the incorporation of deuterium-labelled Phe into proteins in individual live tachyzoites. Our results show a very rapid uptake of L-Phe(D8) by the intracellular growing parasite. T. gondii tachyzoites are capable of extracting L-Phe(D8) from host cells as soon as it invades the cell. L-Phe(D8) from the host cell completely replaces the L-Phe within T. gondii tachyzoites 7–9 hours after infection. A quantitative model based on Raman spectra allowed an estimation of the exchange rate of Phe as 0.5–1.6 × 104 molecules/s. On the other hand, extracellular tachyzoites were not able to consume L-Phe(D8) after 24 hours of infection. These findings further our understanding of the amino acid trafficking between host cells and this strictly intracellular parasite. In particular, this study highlights new aspects of the metabolism of amino acid Phe operative during the interaction between T. gondii and its host cell

Effects of a physical education intervention on cognitive function in young children: randomized controlled pilot study

Randomized controlled trials (RCT) are required to test relationships between physical activity and cognition in children, but these must be informed by exploratory studies. This study aimed to inform future RCT by: conducting practical utility and reliability studies to identify appropriate cognitive outcome measures; piloting an RCT of a 10 week physical education (PE) intervention which involved 2hours per week of aerobically intense PE compared to 2 hours of standard PE (control). 64 healthy children (mean age 6.2 yrs SD 0.3; 33 boys) recruited from 6 primary schools. Outcome measures were the Cambridge Neuropsychological Test Battery (CANTAB), the Attention Network Test (ANT), the Cognitive Assessment System (CAS) and the short form of the Connor’s Parent Rating Scale (CPRS:S). Physical activity was measured habitually and during PE sessions using the Actigraph accelerometer. Test- retest intraclass correlations from CANTAB Spatial Span (r 0.51) and Spatial Working Memory Errors (0.59) and ANT Reaction Time (0.37) and ANT Accuracy (0.60) were significant, but low. Physical activity was significantly higher during intervention vs. control PE sessions (p <0.0001). There were no significant differences between intervention and control group changes in CAS scores. Differences between intervention and control groups favoring the intervention were observed for CANTAB Spatial Span, CANTAB Spatial Working Memory Errors, and ANT Accuracy. The present study has identified practical and age-appropriate cognitive and behavioral outcome measures for future RCT, and identified that schools are willing to increase PE time