Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

Co-directional replication-transcription conflicts lead to replication restart

August 24, 2011Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability1, 2. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional. Virtually all bacteria have the highly expressed ribosomal RNA genes co-directional with replication3. In bacteria, co-directional encounters seem inevitable because the rate of replication is about 10–20-fold greater than the rate of transcription. However, these encounters are generally thought to be benign2, 4, 5, 6, 7, 8, 9. Biochemical analyses indicate that head-on encounters10 are more deleterious than co-directional encounters8 and that in both situations, replication resumes without the need for any auxiliary restart proteins, at least in vitro. Here we show that in vivo, co-directional transcription can disrupt replication, leading to the involvement of replication restart proteins. We found that highly transcribed rRNA genes are hotspots for co-directional conflicts between replication and transcription in rapidly growing Bacillus subtilis cells. We observed a transcription-dependent increase in association of the replicative helicase and replication restart proteins where head-on and co-directional conflicts occur. Our results indicate that there are co-directional conflicts between replication and transcription in vivo. Furthermore, in contrast to the findings in vitro, the replication restart machinery is involved in vivo in resolving potentially deleterious encounters due to head-on and co-directional conflicts. These conflicts probably occur in many organisms and at many chromosomal locations and help to explain the presence of important auxiliary proteins involved in replication restart and in helping to clear a path along the DNA for the replisome.Biotechnology and Biological Sciences Research Council (Great Britain) (Grant BB/E006450/1)Wellcome Trust (London, England) (Grant 091968/Z/10/Z)National Institutes of Health (U.S.) (Grant GM41934)National Institutes of Health (U.S.) (Postdoctoral Fellowship GM093408)Biotechnology and Biological Sciences Research Council (Great Britain) (Sabbatical Visit

The Nature of Abstract Orthographic Codes: Evidence from Masked Priming and Magnetoencephalography

What kind of mental objects are letters? Research on letter perception has mainly focussed on the visual properties of letters, showing that orthographic representations are abstract and size/shape invariant. But given that letters are, by definition, mappings between symbols and sounds, what is the role of sound in orthographic representation? We present two experiments suggesting that letters are fundamentally sound-based representations. To examine the role of sound in orthographic representation, we took advantage of the multiple scripts of Japanese. We show two types of evidence that if a Japanese word is presented in a script it never appears in, this presentation immediately activates the (“actual”) visual word form of that lexical item. First, equal amounts of masked repetition priming are observed for full repetition and when the prime appears in an atypical script. Second, visual word form frequency affects neuromagnetic measures already at 100–130 ms whether the word is presented in its conventional script or in a script it never otherwise appears in. This suggests that Japanese orthographic codes are not only shape-invariant, but also script invariant. The finding that two characters belonging to different writing systems can activate the same form representation suggests that sound identity is what determines orthographic identity: as long as two symbols express the same sound, our minds represent them as part of the same character/letter

A behavioral database for masked form priming

Reading involves a process of matching an orthographic input with stored representations in lexical memory. The masked priming paradigm has become a standard tool for investigating this process. Use of existing results from this paradigm can be limited by the precision of the data and the need for cross-experiment comparisons that lack normal experimental controls. Here, we present a single, large, high-precision, multicondition experiment to address these problems. Over 1,000 participants from 14 sites responded to 840 trials involving 28 different types of orthographically related primes (e.g., castfe–CASTLE) in a lexical decision task, as well as completing measures of spelling and vocabulary. The data were indeed highly sensitive to differences between conditions: After correction for multiple comparisons, prime type condition differences of 2.90 ms and above reached significance at the 5% level. This article presents the method of data collection and preliminary findings from these data, which included replications of the most widely agreed-upon differences between prime types, further evidence for systematic individual differences in susceptibility to priming, and new evidence regarding lexical properties associated with a target word’s susceptibility to priming. These analyses will form a basis for the use of these data in quantitative model fitting and evaluation and for future exploration of these data that will inform and motivate new experiments

Decline of Birds in a Human Modified Coastal Dune Forest Landscape in South Africa

Previous studies demonstrate that old-growth forest remnants and vegetation regenerating after anthropogenic disturbance provide habitat for birds in a human modified coastal dune forest landscape in northern KwaZulu-Natal, South Africa. However, occurrence does not ensure persistence. Based on a 13-year monitoring database we calculated population trends for 37 bird species and general trends in overall bird density in different vegetation types. We evaluated species' characteristics as covariates of population trend and assessed changes in rainfall and proportional area and survey coverage per vegetation type. 76% of species assessed have declined, 57% significantly so at an average rate of 13.9% per year. Overall, bird density has fallen at 12.2% per year across old-growth forest and woody regenerating vegetation types. Changes in proportional area and coverage per vegetation type may partly explain trends for a few species but are unlikely to account for most. Below average rainfall may have contributed to bird declines. However, other possibilities warrant further investigation. Species with larger range extents tended to decline more sharply than did others, and these species may be responding to environmental changes on a broader geographical scale. Our results cast doubt on the future persistence of birds in this human modified landscape. More research is needed to elucidate the mechanisms driving population decline in the study area and to investigate whether the declines identified here are more widespread across the region and perhaps the continent

A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture

Purpose: To evaluate the ability of human airway epithelial cell layers and a simple rat isolated perfused lung (IPL) model to predict pulmonary drug absorption in rats in vivo. Method: The permeability of seven compounds selected to possess a range of lipophilicity was measured in two airway cell lines (Calu-3 and 16HBE14o-), in normal human bronchial epithelial (NHBE) cells and using a simple isolated perfused lungs (IPL) technique. Data from the cell layers and ex vivo lungs were compared to published absorption rates from rat lungs measured in vivo. Results: A strong relationship was observed between the logarithm of the in vivo absorption half-life and the absorption half-life in the IPL (r = 0.97; excluding formoterol). Good log-linear relationships were also found between the apparent first-order absorption rate in vivo and cell layer permeability with correlation coefficients of 0.92, 0.93, 0.91 in Calu-3, 16HBE14o- and NHBE cells, respectively. Conclusion: The simple IPL technique provided a good prediction of drug absorption from the lungs, making it a useful method for empirical screening of drug absorption in the lungs. Permeability measurements were similar in all the respiratory epithelial cell models evaluated, with Calu-3 having the advantage for routine permeability screening purposes of being readily availability, robust and easy to culture

Life histories of the copepods Pseudocalanus minutus, P. acuspes (Calanoida) and Oithona similis (Cyclopoida) in the Arctic Kongsfjorden (Svalbard)

The year-round variation in abundance and stage-specific (vertical) distribution of Pseudocalanus minutus and Oithona similis was studied in the Arctic Kongsfjorden, Svalbard. Maxima of vertically integrated abundance were found in November with 111,297 ind m−2 for P. minutus and 704,633 ind m−2 for O. similis. Minimum abundances comprised 1,088 ind m−2 and 4,483 ind m−2 in June for P. minutus and O. similis, respectively. The congener P. acuspes only occurred in low numbers (15–213 ind m−2), and successful reproduction was debatable. Reproduction of P. minutus took place in May/June, and stage distribution revealed a 1-year life cycle with copepodids CIII, CIV, and CV as the overwintering stages. Oithona similis exhibited two main reproductive peaks in June and August/September, respectively. Moreover, it reproduced more or less continuously throughout the whole year with all stages occurring during the entire sampling period, suggesting two generations per year. Both species migrated towards greater depth in November, but O. similis preferred to stay longer in the upper 100 m as compared to Pseudocalanus. The reproduction of the two species in Kongsfjorden seemed to be linked to phytoplankton dynamics

Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial

Background Osteoarthritis (OA) is the fastest growing cause of disability worldwide. Current treatments for OA are severely limited and a large proportion of people with OA live in constant, debilitating pain. There is therefore an urgent need for novel treatments to reduce pain. Synovitis is highly prevalent in OA and is associated with pain. In inflammatory arthritides such as rheumatoid arthritis, methotrexate (MTX) is the gold standard treatment for synovitis and has a well-known, acceptable toxicity profile. We propose that using MTX to treat patients with symptomatic knee OA will be a practical and safe treatment to reduce synovitis and, consequently, pain. Methods/Design Pain Reduction with Oral Methotrexate in knee Osteoarthritis, a pragmatic phase III trial of Treatment Effectiveness (PROMOTE) is an investigator-initiated, multi-centre, randomized, double-blind, pragmatic placebo-controlled trial. A total of 160 participants with symptomatic knee OA will be recruited across primary and secondary care sites in the United Kingdom and randomized on a 1:1 basis to active treatment or placebo, in addition to usual care, for 12 months. As is usual practice for MTX, dosing will be escalated over six weeks to 25 mg (or maximum tolerated dose) weekly for the remainder of the study. The primary endpoint is change in average knee pain during the past week (measured on an 11-point numerical rating scale) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures. A health economics analysis will also be performed. A magnetic resonance imaging substudy will be conducted to provide an explanatory mechanism for associated symptom change by examining whether MTX reduces synovitis and whether this is related to symptom change. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. Discussion The PROMOTE trial is designed to examine whether MTX is an effective analgesic treatment for OA. The MRI substudy will address the relationship between synovitis and symptom change. This will potentially provide a much needed new treatment for knee OA. Trial registration Current Controlled Trials identifier: ISRCTN77854383 (registered: 25 October 2013)