Exploring how harming and helping behaviors drive prediction and explanation during anthropomorphism

Cacioppo and colleagues advanced the study of anthropomorphism by positing three motives that moderated the occurrence of this phenomenon; belonging, effectance, and explanation. Here, we further this literature by exploring the extent to which the valence of a target’s behavior influences its anthropomorphism when perceivers attempt to explain and predict that target’s behavior, and the involvement of brain regions associated with explanation and prediction in such anthropomorphism. Participants viewed videos of varying visually complex agents - geometric shapes, computer generated (CG) faces, and greebles - in nonrandom motion performing harming and helping behaviors. Across two studies, participants reported a narrative that explained the observed behavior (both studies) while we recorded brain activity (study one), and participants predicted future behavior of the protagonist shapes (study two). Brain regions implicated in prediction error (striatum), not language generation (inferior frontal gyrus; IFG) engaged more to harming than helping behaviors during the anthropomorphism of such stimuli. Behaviorally, we found greater anthropomorphism in explanations of harming rather than helping behaviors, but the opposite pattern when participants predicted the agents’ behavior. Together, these studies build upon the anthropomorphism literature by exploring how the valence of behavior drives explanation and prediction

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

Moonstruck Primates: Owl Monkeys (Aotus) Need Moonlight for Nocturnal Activity in Their Natural Environment

Primates show activity patterns ranging from nocturnality to diurnality, with a few species showing activity both during day and night. Among anthropoids (monkeys, apes and humans), nocturnality is only present in the Central and South American owl monkey genus Aotus. Unlike other tropical Aotus species, the Azara's owl monkeys (A. azarai) of the subtropics have switched their activity pattern from strict nocturnality to one that also includes regular diurnal activity. Harsher climate, food availability, and the lack of predators or diurnal competitors, have all been proposed as factors favoring evolutionary switches in primate activity patterns. However, the observational nature of most field studies has limited an understanding of the mechanisms responsible for this switch in activity patterns. The goal of our study was to evaluate the hypothesis that masking, namely the stimulatory and/or inhibitory/disinhibitory effects of environmental factors on synchronized circadian locomotor activity, is a key determinant of the unusual activity pattern of Azara's owl monkeys. We use continuous long-term (6–18 months) 5-min-binned activity records obtained with actimeter collars fitted to wild owl monkeys (n = 10 individuals) to show that this different pattern results from strong masking of activity by the inhibiting and enhancing effects of ambient luminance and temperature. Conclusive evidence for the direct masking effect of light is provided by data showing that locomotor activity was almost completely inhibited when moonlight was shadowed during three lunar eclipses. Temperature also negatively masked locomotor activity, and this masking was manifested even under optimal light conditions. Our results highlight the importance of the masking of circadian rhythmicity as a determinant of nocturnality in wild owl monkeys and suggest that the stimulatory effects of dim light in nocturnal primates may have been selected as an adaptive response to moonlight. Furthermore, our data indicate that changes in sensitivity to specific environmental stimuli may have been an essential key for evolutionary switches between diurnal and nocturnal habits in primates

A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation.

BACKGROUND: The mammalian DNA-damage response (DDR) has evolved to protect genome stability and maximize cell survival following DNA-damage. One of the key regulators of the DDR is p53, itself tightly regulated by MDM2. Following double-strand DNA breaks (DSBs), mediators including ATM are recruited to the site of DNA-damage. Subsequent phosphorylation of p53 by ATM and ATM-induced CHK2 results in p53 stabilization, ultimately intensifying transcription of p53-responsive genes involved in DNA repair, cell-cycle checkpoint control and apoptosis. METHODS: In the current study, we investigated the stabilization and activation of p53 and associated DDR proteins in response to treatment of human colorectal cancer cells (HCT116p53+/+) with the MDM2 antagonist, Nutlin-3. RESULTS: Using immunoblotting, Nutlin-3 was observed to stabilize p53, and activate p53 target proteins. Unexpectedly, Nutlin-3 also mediated phosphorylation of p53 at key DNA-damage-specific serine residues (Ser15, 20 and 37). Furthermore, Nutlin-3 induced activation of CHK2 and ATM - proteins required for DNA-damage-dependent phosphorylation and activation of p53, and the phosphorylation of BRCA1 and H2AX - proteins known to be activated specifically in response to DNA damage. Indeed, using immunofluorescent labeling, Nutlin-3 was seen to induce formation of γH2AX foci, an early hallmark of the DDR. Moreover, Nutlin-3 induced phosphorylation of key DDR proteins, initiated cell cycle arrest and led to formation of γH2AX foci in cells lacking p53, whilst γH2AX foci were also noted in MDM2-deficient cells. CONCLUSION: To our knowledge, this is the first solid evidence showing a secondary role for Nutlin-3 as a DDR triggering agent, independent of p53 status, and unrelated to its role as an MDM2 antagonist

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

In silico-designed lignin peroxidase from Phanerochaete chrysosporium shows enhanced acid stability for depolymerization of lignin

Background: The lignin peroxidase isozyme H8 from the white-rot fungus Phanerochaete chrysosporium (LiPH8) demonstrates a high redox potential and can efficiently catalyze the oxidation of veratryl alcohol, as well as the degradation of recalcitrant lignin. However, native LiPH8 is unstable under acidic pH conditions. This characteristic is a barrier to lignin depolymerization, as repolymerization of phenolic products occurs simultaneously at neutral pH. Because repolymerization of phenolics is repressed at acidic pH, a highly acid-stable LiPH8 could accelerate the selective depolymerization of recalcitrant lignin. Results: The engineered LiPH8 was in silico designed through the structural superimposition of surface-active site-harboring LiPH8 from Phanerochaete chrysosporium and acid-stable manganese peroxidase isozyme 6 (MnP6) from Ceriporiopsis subvermispora. Effective salt bridges were probed by molecular dynamics simulation and changes to Gibbs free energy following mutagenesis were predicted, suggesting promising variants with higher stability under extremely acidic conditions. The rationally designed variant, A55R/N156E-H239E, demonstrated a 12.5-fold increased half-life under extremely acidic conditions, 9.9-fold increased catalytic efficiency toward veratryl alcohol, and a 7.8-fold enhanced lignin model dimer conversion efficiency compared to those of native LiPH8. Furthermore, the two constructed salt bridges in the variant A55R/N156E-H239E were experimentally confirmed to be identical to the intentionally designed LiPH8 variant using X-ray crystallography (PDB ID: 6A6Q). Conclusion: Introduction of strong ionic salt bridges based on computational design resulted in a LiPH8 variant with markedly improved stability, as well as higher activity under acidic pH conditions. Thus, LiPH8, showing high acid stability, will be a crucial player in biomass valorization using selective depolymerization of lignin

Confirmation of the Chinese version of the Problematic Internet Use Questionnaire Short Form (PIUQ-SF)

Although an increasing number of studies have focused on problematic Internet use, numerous measures exist with only modest investigation into their reliability and validity, both within and across different cultures (Király et al. 2015). The most frequently used questionnaire is the Internet Addiction Test (Young 1998). However, its factor structure appears to be unstable (e.g., Fernandez-Villa et al. 2015; Pontesetal. 2014). Koronczai et al. (2011) suggested that a suitable measure should fit six basic requirements. More specifically, it should be (i) comprehensive, that is examining more, possibly all, aspects of problematic Internet use; (ii) as concise as possible, in order to be able to assess the more impulsive population, and to use in time-limited surveys (or having different forms with different length). Such a measure should be (iii) reliable and valid for different methods of data collection (e.g. online, paper-and-pencil self-rating, face-to-face); as well as (iv) for different age groups (e.g. adolescents and adults), and (v) in different cultural settings. Finally, (vi) cut-off scores should be defined on the basis of clinical examination. The Problematic Internet Use Questionnaire (PIUQ) (Demetrovics et al. 2008) fulfills several of the aforementioned criteria. The 18-item PIUQ is a comprehensive measure that assesses three basic aspects of problematic Internet use (i.e., obsession, neglect, and control disorder). The 18-item and the shorter 9-item versions of the PIUQ have a reliable structure, and are suitable for time-limited surveys and have proved to be valid across various methods of data collection (i.e., online as well as paper-pencil) and age groups (Demetrovics et al. 2008; Koronczai et al. 2011). However, its implementation has so far mostly taken place in Western individualistic cultures (Kelley and Gruber 2010, 2013; Koronczai et al. 2011; Zahodne et al. 2011. To date, the PIUQ has also been applied in a survey in Iran with good Cronbach’s alpha coefficients and subscales (Mazhari 2012a, 2012b). Consequently, validation of the questionnaire in a culture that is significantly different from the Western culture is needed. Accordingly, the aim of the present study was the validation of the 9-item PIUQ among the Chinese population

Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205+ dendritic cells

Two major distinct subsets of dendritic cells (DCs) are arranged to regulate our immune responses in vivo; 33D1+ and DEC-205+ DCs. Using anti-33D1-specific monoclonal antibody, 33D1+ DCs were successfully depleted from C57BL/6 mice. When 33D1+ DC-depleted mice were stimulated with LPS, serum IL-12, but not IL-10 secretion that may be mediated by the remaining DEC-205+ DCs was markedly enhanced, which may induce Th1 dominancy upon TLR signaling. The 33D1+ DC-depleted mice, implanted with syngeneic Hepa1-6 hepatoma or B16-F10 melanoma cells into the dermis, showed apparent inhibition of already established tumor growth in vivo when they were subcutaneously (sc) injected once or twice with LPS after tumor implantation. Moreover, the development of lung metastasis of B16-F10 melanoma cells injected intravenously was also suppressed when 33D1+ DC-deleted mice were stimulated twice with LPS in a similar manner, in which the actual cell number of NK1.1+CD3− NK cells in lung tissues was markedly increased. Furthermore, intraperitoneal (ip) administration of a very small amount of melphalan (l-phenylalanine mustard; l-PAM) (0.25 mg/kg) in LPS-stimulated 33D1+ DC-deleted mice helped to induce H-2Kb-restricted epitope-specific CD8+ cytotoxic T lymphocytes (CTLs) among tumor-infiltrating lymphocytes against already established syngeneic E.G7-OVA lymphoma. These findings indicate the importance and effectiveness of selective targeting of a specific subset of DCs, such as DEC-205+ DCs alone or with a very small amount of anticancer drugs to activate both CD8+ CTLs and NK effectors without externally added tumor antigen stimulation in vivo and provide a new direction for tumor immunotherapy

Revisiting Estimates of CTL Killing Rates In Vivo

Recent experimental advances have allowed the estimation of the in vivo rates of killing of infected target cells by cytotoxic T lymphocytes (CTL). We present several refinements to a method applied previously to quantify killing of targets in the spleen using a dynamical model. We reanalyse data previously used to estimate killing rates of CTL specific for two epitopes of lymphocytic choriomeningitis virus (LCMV) in mice and show that, contrary to previous estimates the “killing rate” of effector CTL is approximately twice that of memory CTL. Further, our method allows the fits to be visualized, and reveals one potentially interesting discrepancy between fits and data. We discuss extensions to the basic CTL killing model to explain this discrepancy and propose experimental tests to distinguish between them