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Rapid individual cognitive phenotyping holds the potential to revolutionize domains as wide-ranging as personalized learning, employment practices, and precision psychiatry. Going beyond limitations imposed by traditional lab-based experiments, new efforts have been underway towards greater ecological validity and participant diversity to capture the full range of individual differences in cognitive abilities and behaviors across the general population. Building on this, we developed Skill Lab, a novel game-based tool that simultaneously assesses a broad suite of cognitive abilities while providing an engaging narrative. Skill Lab consists of six mini-games as well as 14 established cognitive ability tasks. Using a popular citizen science platform (N = 10725), we conducted a comprehensive validation in the wild of a game-based cognitive assessment suite. Based on the game and validation task data, we constructed reliable models to simultaneously predict eight cognitive abilities based on the users' in-game behavior. Follow-'-up validation tests revealed that the models can discriminate nuances contained within each separate cognitive ability as well as capture a shared main factor of generalized cognitive ability. Our game-based measures are five times faster to complete than the equivalent task-based measures and replicate previous findings on the decline of certain cognitive abilities with age in our large cross-sectional population sample (N = 6369). Taken together, our results demonstrate the feasibility of rapid in-the-wild systematic assessment of cognitive abilities as a promising first step towards population-scale benchmarking and individualized mental health diagnostics., 24 pages, 8 figures, and 4 tables. Supplementary Information: osf.io/pnw5z//

We present the results of an exploratory player experience study on the game Quantum Moves, a citizen science game where players move quantum particles to help create a quantum computer. Eight-hundred-and-seventeen players responded to a 13-question exploratory survey constructed to understand how players relate to the game, what are their motivations, and how could the game be improved. We analyzed the data using descriptive statistics and thematic analysis. Specifically, the thematic analysis helped identifying two cross-cutting themes amongst the players: (a) learning and (b) the opportunity to contribute to science. Results indicate that the opportunity to help science, along with game design, game elements, involvement of players with the scientific community, and players’ strategies influence experience. Implications of the particular findings for the research on player experience on citizen science games and development of evaluation methods are discussed.

Membranes not only provide cellular compartmentalization but influence protein behavior and folding by virtue of the multitude of different lipid types. We have studied the impact of lipid composition on the folding of the membrane-associated protein Mistic from B. subtilis. We use dimerisation via the single Cys3 residue as monitor for the degree of correct folding, since mis- or unfolding will expose the otherwise buried Cys3. We find great variability in how lipids affect protein production and dimerization, ranging from high production and low dimerization via increased production and higher dimerization to low production and low dimerization. Phosphocholine (PC) vesicles, in particular di-oleoyl-PC, lead to the highest production levels. Shorter chain lengths lead to reduced production but higher levels of dimerization. Different lipids may promote correct folding of Mistic to different extents, mediated by proper hydrophobic matching (attained for long-chain but not short-chain PC vesicles) and the existence of a fluid phase (the gel phase reduces production as well as dimerization, probably by immobilizing Mistic on the surface). The very fact that different lipids have an effect indicates that Mistic behaves like a bona fide membrane protein with a clear preference for membranes of a certain thickness and flexibility.

In higher education (HE), science and technology (STEM) institutions were early adopters of entrepreneurship education, recognizing that STEM majors in particular have a disproportional potential to form high-growth ventures in high-tech industries with high-value prospects. Yet, only limited empirical work has been carried out to shed light on how these programs are developed and how and why they are designed and organized the way that they are. What we do know typically comes to us from single-case reports on isolated programs. This study aims to provide deeper insights through an innovative and comprehensive research design that provides a way to compare and contrast case studies of five programs, developed by different educators, in different Nordic nations, and at different HE STEM institutions. The study mainly aims to explore how these cross-case and cross-national studies can guide future entrepreneurship education program development. However, considering the deliberate selection of comparable cases, this study finds a striking diversity in effective and successful programs, and uncovers strong interdependencies between program design and inception and the program developers. As such, in addition to providing guidance for program developers, the study identifies implications for other stakeholders, including students, university management, and entrepreneurship education research.

Mutations in the human TGFBI gene encoding TGFBIp have been linked to protein deposits in the cornea leading to visual impairment. The protein consists of an N-terminal Cys-rich EMI domain and four consecutive fasciclin 1 (FAS1) domains. We have compared the stabilities of wild-type (WT) human TGFBIp and six mutants known to produce phenotypically distinct deposits in the cornea. Amino acid substitutions in the first FAS1 (FAS1-1) domain (R124H, R124L, and R124C) did not alter the stability. However, substitutions within the fourth FAS1 (FAS1-4) domain (A546T, R555Q, and R555W) affected the overall stability of intact TGFBIp revealing the following stability ranking R555W>WT>R555Q>A546T. Significantly, the stability ranking of the isolated FAS1-4 domains mirrored the behavior of the intact protein. In addition, it was linked to the aggregation propensity as the least stable mutant (A546T) forms amyloid fibrils while the more stable variants generate non-amyloid amorphous deposits in vivo. Significantly, the data suggested that both an increase and a decrease in the stability of FAS1-4 may unleash a disease mechanism. In contrast, amino acid substitutions in FAS1-1 did not affect the stability of the intact TGFBIp suggesting that molecular the mechanism of disease differs depending on the FAS1 domain carrying the mutation.

Human transforming growth factor β induced protein (TGFBIp) is composed of 683 residues, including an N-terminal cysteine-rich (EMI) domain, four homologous fasciclin domains, and an Arg-Gly-Asp (RGD) motif near the C-terminus. The protein is of interest because mutations in the TGFBI gene encoding TGFBIp lead to corneal dystrophy (CD), a condition where protein aggregates within the cornea compromise transparency. The complete three-dimensional structure of TGFBIp is not yet available, with the exception of a partial X-ray structure of the archetype FAS1 domain derived from Drosophila fasciclin-1. In this study, small-angle X-ray scattering (SAXS) models of intact wild-type (WT) human TGFBIp and a mutant (R124H) are presented. The mutation R124H leads to a variant of granular CD. The deduced structure of the TGFBIp monomer consists of four FAS1 domains in a simple “beads-on-a-string” arrangement, constructed by the superimposition of four consecutive Drosophila fasciclin domains. The SAXS-based model of the TGFBIp R124H mutant displayed no structural differences from WT. Both WT TGFBIp and the R124H mutant formed trimers at higher protein concentrations. The similar association properties and three-dimensional shape of the two proteins suggest that the mutation does not induce any major structural rearrangements, but points towards the role of other corneal-specific factors in the formation of corneal R124H deposits.

Cells are under constant onslaught from several intrinsic and extrinsic stressors, which lead to the occurrence and accumulation of molecular damage, functional impairment, aging, and eventual death. Protein misfolding is both a cause and a consequence of increased cellular stress. An age-related failure of the complex systems for handling protein misfolding results in the accumulation of misfolded and aggregated proteins, and consequent conformational diseases. However, some misfolded proteins have been found to be both toxic and, in some cases, protective, highlighting the various complex, dynamic, and interdependent mechanisms at play. Molecular mechanisms are being elucidated for the occurrence of protein misfolding and for its prevention by chaperones and various pathways of degradation. Insights from the knowledge about proteodynamics are likely to impact future interventional strategies to counter stress and to promote healthy aging by preventing and/or treatment of protein conformational diseases.

Cells are under constant onslaught from several intrinsic and extrinsic stressors, which lead to the occurrence and accumulation of molecular damage, functional impairment, aging, and eventual death. Protein misfolding is both a cause and a consequence of increased cellular stress. An age-related failure of the complex systems for handling protein misfolding results in the accumulation of misfolded and aggregated proteins, and consequent conformational diseases. However, some misfolded proteins have been found to be both toxic and, in some cases, protective, highlighting the various complex, dynamic, and interdependent mechanisms at play. Molecular mechanisms are being elucidated for the occurrence of protein misfolding and for its prevention by chaperones and various pathways of degradation. Insights from the knowledge about proteodynamics are likely to impact future interventional strategies to counter stress and to promote healthy aging by preventing and/or treatment of protein conformational diseases.

The eye being our window to the world and one of the major components of our neurological system as well, like any other part of the body, is also affected by aging. The eye is one of the oldest remnants of evolution, and its importance can be seen from the fact that even evolutionarily primitive organisms had some rudimentary form of an eye. However, vision is one of those aspects of life that are easily taken for granted, and it is only when one starts to lose vision that one realises its importance. Understanding agerelated changes of the eye and the consequent diseases of the eye during aging is an extremely important issue with respect to any discussion about improving the quality of life in old age. Therefore, this book is a welcome and timely contribution towards that goal. The book is a compilation of 22 well-written chapters by 30 authors involved in basic research and clinical management of the problems of the aging eye. Although the book has not been clearly divided into identifiable sections as such, one could group the chapters in two major sections. The first group is the one in which each chapter describes one particular structure of the eye and its development and the telltale signs of aging, and the second group contains articles with a clinical focus dealing with one or more diseases of the eye. The last couple of chapters deal with practical suggestions and advice for the rehabilitation of low vision people, and for the protection of the eyes in the elderly. Cellular aging in the eye and its relevance to eye diseases is an issue that is only beginning to be looked at in detail. Therefore, the first chapter by L. Cerulli gives an overview of aging as the major risk factor in eye disease, and also discusses the more subtle changes that take place within the eye that are not easily visible but still impact a lot on the eye’s capacity to heal itself. Chapter 2 by J. Fehr and Z. Olah deals with the first obvious external part of the eye, the eyelid—one of the tissues that visibly show the effects of aging. A feature of the book in general is that no structure of the eye, be it the eyelid, or the lens or the retina and so on, is given preference over the other, and a balanced treatment is maintained. Another point worth mentioning is that in line with the systematic nature of the chapters, the first few chapters systematically take you through each of the important structures of the eye starting from the outside and then going on to the inside and innermost parts of the eye. Thus the editors have, in effect, created a visual map for the reader, and the visualisation works just like a ray of light that first enters the eye through the cornea, followed by its passage through the lens, the iris, the vitreous, and the retina until it hits the nervous system. Chapter 3 by P. Artal describes the general optics of the eye and the effect of normal aging on these optics. The real journey into the R. V. Basaiawmoit (&) S. I. S. Rattan Deparment of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, 8000 Aarhus, Denmark e-mail: rvb@inano.dk

Quantum Moves is a citizen science game that investigates the ability of humans to solve complex physics challenges that are intractable for computers. During the launch of Quantum Moves in April 2016 the game's leaderboard function broke down resulting in a "no leaderboard" game experience for some players for a couple of days (though their scores were still displayed). The subsequent quick fix of an all-time Top 5 leaderboard, and the following long-term implementation of a personalized relative-position (infinite) leaderboard provided us with a unique opportunity to compare and investigate the effect of different leaderboard implementations on player performance in a points-driven citizen science game. All three conditions were live sequentially during the game's initial influx of more than 150.000 players that stemmed from global press attention on Quantum Moves due the publication of a Nature paper about the use of Quantum Moves in solving a specific quantum physics problem. Thus, it has been possible to compare the three conditions and their influence on the performance (defined as a player's quality of game play related to a high-score) of over 4500 new players. These 4500 odd players in our three leaderboard-conditions have a similar demographic background based upon the time-window over which the implementations occurred and controlled against Player ID tags. Our results placed Condition 1 experience over condition 3 and in some cases even over condition 2 which goes against the general assumption that leaderboards enhance gameplay and its subsequent overuse as a an oft-relied upon element that designers slap onto a game to enhance said appeal. Our study thus questions the use of leaderboards as general performance enhancers in gamification contexts and brings some empirical rigor to an often under-reported but overused phenomenon., 8 pages, 3 figures, accepted for publication at ECGBL