259 research outputs found

    Трехизбенский городок в исторических источниках

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    Contains fulltext : 137371.pdf (publisher's version ) (Closed access)The role of face typicality in face recognition is well established, but it is unclear whether face typicality is important for face evaluation. Prior studies have focused mainly on typicality's influence on attractiveness, although recent studies have cast doubt on its importance for attractiveness judgments. Here, we argue that face typicality is an important factor for social perception because it affects trustworthiness judgments, which approximate the basic evaluation of faces. This effect has been overlooked because trustworthiness and attractiveness judgments have a high level of shared variance for most face samples. We show that for a continuum of faces that vary on a typicality-attractiveness dimension, trustworthiness judgments peak around the typical face. In contrast, perceived attractiveness increases monotonically past the typical face, as faces become more like the most attractive face. These findings suggest that face typicality is an important determinant of face evaluation.9 p

    White Look-Alikes: Mainstream Culture Adoption Makes Immigrants "Look" Phenotypically White

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    White Americans generally equate "being American" with "being White." In six studies, we demonstrate that White Americans perceive immigrants who adopt American mainstream culture as racially White and, reciprocally, perceive White-looking immigrants as assimilating more. In Studies 1 and 2, participants visually represented immigrants who adopted U.S. culture by acculturating to mainstream American culture or by holding a common or dual identity as more phenotypically White and less stereotypic in appearance. In Studies 3 and 4, these processes explained why participants were less likely to racially profile immigrants but also regarded them as less qualified for integration support. In Study 5, participants perceived light skin to fit to high U.S. culture adoption and dark skin to low U.S. culture adoption. Finally, in Study 6, light-skinned immigrants were seen as less threatening because they were perceived as assimilating more. Immigrants’ acculturation orientation and appearance interact and shape how they are evaluated

    О номенклатуре Ceramium rubrum (Rhodophyta)

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    Анализируются номенклатурные проблемы, связанные с цитацией видового названия Ceramium rubrum auctorum. Показано, что правильным названием данного таксона следует считать C. virgatum Roth.A nomenclature problems of misuse of a species name Ceramium rubrum auctorum are analyzed. The correct name of the taxon is demonstrated to be C. virgatum Roth

    Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype

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    Natural product (NP)-inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo-natural products (PNPs) are de novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the design and synthesis of apoxidoles, a novel pseudo-NP class, whereby indole- and tetrahydropyridine fragments are linked in monopodal connectivity not found in nature. Apoxidoles are efficiently accessible by an enantioselective [4+2] annulation reaction. Biological evaluation revealed that apoxidoles define a new potent type IV inhibitor chemotype of indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme considered a target for the treatment of neurodegeneration, autoimmunity and cancer. Apoxidoles target apo-IDO1, prevent heme binding and induce unique amino acid positioning as revealed by crystal structure analysis. Novel type IV apo-IDO1 inhibitors are in high demand, and apoxidoles may provide new opportunities for chemical biology and medicinal chemistry research

    Disease-related p63 DBD mutations impair DNA binding by distinct mechanisms and varying degree

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    : The transcription factor p63 shares a high sequence identity with the tumour suppressor p53 which manifests itself in high structural similarity and preference for DNA sequences. Mutations in the DNA binding domain (DBD) of p53 have been studied in great detail, enabling a general mechanism-based classification. In this study we provide a detailed investigation of all currently known mutations in the p63 DBD, which are associated with developmental syndromes, by measuring their impact on transcriptional activity, DNA binding affinity, zinc binding capacity and thermodynamic stability. Some of the mutations we have further characterized with respect to their ability to convert human dermal fibroblasts into induced keratinocytes. Here we propose a classification of the p63 DBD mutations based on the four different mechanisms of DNA binding impairment which we identified: direct DNA contact, zinc finger region, H2 region, and dimer interface mutations. The data also demonstrate that, in contrast to p53 cancer mutations, no p63 mutation induces global unfolding and subsequent aggregation of the domain. The dimer interface mutations that affect the DNA binding affinity by disturbing the interaction between the individual DBDs retain partial DNA binding capacity which correlates with a milder patient phenotype

    Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis

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    Concurrent mutation of a RAS oncogene and the tumor suppressor p53 is common in tumorigenesis, and inflammation can promote RAS-driven tumorigenesis without the need to mutate p53. Here, we show, using a well-established mutant RAS and an inflammation-driven mouse skin tumor model, that loss of the p53 inhibitor iASPP facilitates tumorigenesis. Specifically, iASPP regulates expression of a subset of p63 and AP1 targets, including genes involved in skin differentiation and inflammation, suggesting that loss of iASPP in keratinocytes supports a tumor-promoting inflammatory microenvironment. Mechanistically, JNK-mediated phosphorylation regulates iASPP function and inhibits iASPP binding with AP1 components, such as JUND, via PXXP/SH3 domain-mediated interaction. Our results uncover a JNK-iASPP-AP1 regulatory axis that is crucial for tissue homeostasis. We show that iASPP is a tumor suppressor and an AP1 coregulator

    Quantifying the informational value of classification images

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    Reverse correlation is an influential psychophysical paradigm that uses a participant’s responses to randomly varying images to build a classification image (CI), which is commonly interpreted as a visualization of the participant’s mental representation. It is unclear, however, how to statistically quantify the amount of signal present in CIs, which limits the interpretability of these images. In this article, we propose a novel metric, infoVal, which assesses informational value relative to a resampled random distribution and can be interpreted like a z score. In the first part, we define the infoVal metric and show, through simulations, that it adheres to typical Type I error rates under various task conditions (internal validity). In the second part, we show that the metric correlates with markers of data quality in empirical reverse-correlation data, such as the subjective recognizability, objective discriminability, and test–retest reliability of the CIs (convergent validity). In the final part, we demonstrate how the infoVal metric can be used to compare the informational value of reverse-correlation datasets, by comparing data acquired online with data acquired in a controlled lab environment. We recommend a new standard of good practice in which researchers assess the infoVal scores of reverse-correlation data in order to ensure that they do not read signal in CIs where no signal is present. The infoVal metric is implemented in the open-source rcicr R package, to facilitate its adoption

    Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis

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    Concurrent mutation of a RAS oncogene and the tumor suppressor p53 is common in tumorigenesis, and inflammation can promote RAS-driven tumorigenesis without the need to mutate p53. Here, we show, using a well-established mutant RAS and an inflammation-driven mouse skin tumor model, that loss of the p53 inhibitor iASPP facilitates tumorigenesis. Specifically, iASPP regulates expression of a subset of p63 and AP1 targets, including genes involved in skin differentiation and inflammation, suggesting that loss of iASPP in keratinocytes supports a tumor-promoting inflammatory microenvironment. Mechanistically, JNK-mediated phosphorylation regulates iASPP function and inhibits iASPP binding with AP1 components, such as JUND, via PXXP/SH3 domain-mediated interaction. Our results uncover a JNK-iASPP-AP1 regulatory axis that is crucial for tissue homeostasis. We show that iASPP is a tumor suppressor and an AP1 coregulator

    Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites

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    The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have critical impact on centrosome stability and lead to mitotic centrosome fragmentation and unbalanced chromosome segregation. Our findings identify doryphagy as an important centrosome-regulating pathway and bring mechanistic insights to the link between autophagy dysfunction and chromosomal instability. In addition, we highlight the vital role of centriolar satellites in maintaining centrosome integrity

    Faces, people and the brain : the 45th Sir Frederic Bartlett lecture

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    The fact that the face is a source of diverse social signals allows us to use face and person perception as a model system for asking important psychological questions about how our brains are organised. A key issue concerns whether we rely primarily on some form of generic representation of the common physical source of these social signals (the face) to interpret them, or instead create multiple representations by assigning different aspects of the task to different specialist components. Variants of the specialist components hypothesis have formed the dominant theoretical perspective on face perception for more than three decades, but despite this dominance of formally and informally expressed theories the underlying principles and extent of any division of labour remain uncertain. Here, I discuss three important sources of constraint. First, the evolved structure of the brain. Second, the need to optimise responses to different everyday tasks. Third, the statistical structure of faces in the perceiver's environment. I show how these constraints interact to determine the underlying functional organisation of face and person perception
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