Metacognition and Abstract Concepts

The problem of how concepts can refer to or be about the non‐mental world is particularly puzzling for abstract concepts. There is growing evidence that many characteristics beyond the perceptual are involved in grounding different kinds of abstract concept. A resource that has been suggested, but little explored, is introspection. This paper develops that suggestion by focusing specifically on metacognition—on the thoughts and feelings that thinkers have about a concept. One example of metacognition about concepts is the judgement that we should defer to others in how a given concept is used. Another example is our internal assessment of which concepts are dependable and useful, and which less so. Metacognition of this kind may be especially important for grounding abstract concepts

Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes

Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. At the molecular level, the sole relevant interaction is that FITMs directly bind to triacyglycerol and diacylglycerol, but how they function at the molecular level is not known.Saccharomyces cerevisiaehas two FITM homologues: Scs3p and Yft2p. Scs3p was initially identified because deletion leads to inositol auxotrophy, with an unusual sensitivity to addition of choline. This strongly suggests a role for Scs3p in phospholipid biosynthesis. Looking at the FITM family as widely as possible, we found that FITMs are widespread throughout eukaryotes, indicating presence in the last eukaryotic common ancestor. Protein alignments also showed that FITM sequences contain the active site of lipid phosphatase/phosphotransferase (LPT) enzymes. This large family transfers phosphate-containing headgroups either between lipids or in exchange for water. We confirmed the prediction that FITMs are related to LPTs by showing that single amino-acid substitutions in the presumptive catalytic site prevented their ability to rescue growth of the mutants on low inositol/high choline media when over-expressed. The substitutions also prevented rescue of other phenotypes associated with loss of FITM in yeast, including mistargeting of Opi1p, defective ER morphology, and aberrant lipid droplet budding. These results suggest that Scs3p, Yft2p and FITMs in general are LPT enzymes involved in an as yet unknown critical step in phospholipid metabolism

mTCTScan: a comprehensive platform for annotation and prioritization of mutations affecting drug sensitivity in cancers

Cancer therapies have experienced rapid progress in recent years, with a number of novel small-molecule kinase inhibitors and monoclonal antibodies now being widely used to treat various types of human cancers. During cancer treatments, mutations can have important effects on drug sensitivity. However, the relationship between tumor genomic profiles and the effectiveness of cancer drugs remains elusive. We introduce Mutation To Cancer Therapy Scan (mTCTScan) web server (http://jjwanglab.org/mTCTScan) that can systematically analyze mutations affecting cancer drug sensitivity based on individual genomic profiles. The platform was developed by leveraging the latest knowledge on mutation-cancer drug sensitivity associations and the results from large-scale chemical screening using human cancer cell lines. Using an evidence-based scoring scheme based on current integrative evidences, mTCTScan is able to prioritize mutations according to their associations with cancer drugs and preclinical compounds. It can also show related drugs/compounds with sensitivity classification by considering the context of the entire genomic profile. In addition, mTCTScan incorporates comprehensive filtering functions and cancer-related annotations to better interpret mutation effects and their association with cancer drugs. This platform will greatly benefit both researchers and clinicians for interrogating mechanisms of mutation-dependent drug response, which will have a significant impact on cancer precision medicine.published_or_final_versio

No transfer of calibration between action and perception in learning a golf putting task

We assessed calibration of perception and action in the context of a golf putting task. Previous research has shown that right-handed novice golfers make rightward errors both in the perception of the perfect aiming line from the ball to the hole and in the putting action. Right-handed experts, however, produce accurate putting actions but tend to make leftward errors in perception. In two experiments, we examined whether these skill-related differences in directional error reflect transfer of calibration from action to perception. In the main experiment, three groups of right-handed novice participants followed a pretest, practice, posttest, retention test design. During the tests, directional error for the putting action and the perception of the perfect aiming line were determined. During practice, participants were provided only with verbal outcome feedback about directional error; one group trained perception and the second trained action, whereas the third group did not practice. Practice led to a relatively permanent annihilation of directional error, but these improvements in accuracy were specific to the trained task. Hence, no transfer of calibration occurred between perception and action. The findings are discussed within the two-visual-system model for perception and action, and implications for perceptual learning in action are raised

Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Violent video games and morality: a meta-ethical approach

This paper considers what it is about violent video games that leads one reasonably minded person to declare "That is immoral" while another denies it. Three interpretations of video game content a re discussed: reductionist, narrow, and broad. It is argued that a broad interpretation is required for a moral objection to be justified. It is further argued that understanding the meaning of moral utterances – like "x is immoral" – is important to an understanding of why there is a lack of moral consensus when it comes to the content of violent video games. Constructive ecumenical expressivism is presented as a means of explaining what it is that we are doing when we make moral pronouncements and why, when it comes to video game content, differing moral attitudes abound. Constructive ecumenical expressivism is also presented as a means of illuminating what would be required for moral consensus to be achieved

The aesthetic stance - on the conditions and consequences of becoming a beholder

What does it mean to be an aesthetic beholder? Is it different than simply being a perceiver? Most theories of aesthetic perception focus on 1) features of the perceived object and its presentation or 2) on psychological evaluative or emotional responses and intentions of perceiver and artist. In this chapter I propose that we need to look at the process of engaged perception itself, and further that this temporal process of be- coming a beholder must be understood in its embodied, contextual and dynamic speci- ficity. Through both phenomenological and neuroscientific explorations I analyze what is characteristic about a more “aesthetic stance” and argue that there is a certain asym- metry between beholder and beheld, which has to do with a disengagement of goal- directed action, and which allows for other kinds of perceptual involvement than in a more “practical stance”. It is a multi-disciplinary project integrating a sensorimotor no- tion of aesthetic affordances, 18th century philosophy, and large-scale brain network findings. What ensues is a new dynamic framework for future empirical and theoretical research on aesthetic perception

Evolutionary psychology and morality. Review essay

Evolution has since the publication of The origin of species (1859) been a source of inspiration, and a bone of contention, not only for biology but also for philosophy and the sciences of man. The moral consequences of Darwinism have been a concern for ethicists since Herbert Spencer elevated the survival of the fittest to a norm underwriting cultural an