Action anticipation through attribution of false belief by 2 year olds

Two-year-olds engage in many behaviors that ostensibly require the attribution of mental states to other individuals. Yet the overwhelming consensus has been that children of this age are unable to attribute false beliefs. In the current study, we used an eyetracker to record infants' looking behavior while they watched actions on a computer monitor. Our data demonstrate that 25-month-old infants correctly anticipate an actor's actions when these actions can be predicted only by attributing a false belief to the actor

Agent-based computational modeling of wounded epithelial cell monolayers

Computational modeling of biological systems, or ‘in silico biology’ is an emerging tool for understanding structure and order in biological tissues. Computational models of the behavior of epithelial cells in monolayer cell culture have been developed and used to predict the healing characteristics of scratch wounds made to urothelial cell cultures maintained in low and physiological [Ca2+] environments. Both computational models and in vitro experiments demonstrated that in low exogenous [Ca2+], the closure of 500mm scratch wounds was achieved primarily by cell migration into the denuded area. The wound healing rate in low (0.09mM) [Ca2+] was approximately twice as rapid as in physiological (2mM) [Ca2+]. Computational modeling predicted that in cell cultures that are actively proliferating, no increase in the fraction of cells in S-phase would be expected, and this conclusion was supported experimentally in vitro by BrdU incorporation assay. We have demonstrated that a simple rule-based model of cell behavior, incorporating rules relating to contact inhibition of proliferation and migration, is sufficient to qualitatively predict the calcium-dependent pattern of wound closure observed in vitro. Differences between the in vitro and in silico models suggest a role for wound-induced signaling events in urothelial cell cultures

Sources of variability in cytosolic calcium transients triggered by stimulation of homogeneous uro-epithelial cell monolayers

Epithelial tissue structure is the emergent outcome of the interactions between large numbers of individual cells. Experimental cell biology offers an important tool to unravel these complex interactions, but current methods of analysis tend to be limited to mean field approaches or representation by selected subsets of cells. This may result in bias towards cells that respond in a particular way and/or neglect local, context-specific cell responses. Here, an automated algorithm was applied to examine in detail the individual calcium transients evoked in genetically homogeneous, but asynchronous populations of cultured non-immortalized normal human urothelial cells when subjected to either the global application of an external agonist or a localized scratch wound. The recorded calcium transients were classified automatically according to a set of defined metrics and distinct sub-populations of cells that responded in qualitatively different ways were observed. The nature of this variability in the homogeneous cell population was apportioned to two sources: intrinsic variation in individual cell responses and extrinsic variability due to context-specific factors of the environment, such as spatial heterogeneity. Statistically significant variation in the features of the calcium transients evoked by scratch wounding according to proximity to the wound edge was identified. The manifestation of distinct sub-populations of cells is considered central to the coordination of population-level response resulting in wound closure

Investing in Biodiversity Conservation: Proceedings of a Workshop

This document presents the proceedings of a one-day Workshop on Investing in Biodiversity Conservation held at the Inter-American Development Bank in Washington, D.C., on October 28, 1996. The first part of the workshop was dedicated to the presentation of key topics on biodiversity financing by five leaders in the field. The second part of the workshop was dedicated to a discussion and exchange of ideas on the role of the IDB in investing in biodiversity conservation. Three main recommendations emerged: 1) The Bank should prepare a report on on its experience in biodiversity projects and development programs with biodiversity components; 2) A task force should be formed to work on a bio-diversity policy or strategy; 3) IDB staff should be trained to understand the biodiversity concept and its implications in project preparation and implementation.Environmental Policy, Biodiversity, Natural Resources Management

The Human Tissue-Biomaterial Interface : A Role for PPARγ-Dependent Glucocorticoid Receptor Activation in Regulating the CD163(+) M2 Macrophage Phenotype

In vivo studies of implanted acellular biological scaffolds in experimental animals have shown constructive remodeling mediated by anti-inflammatory macrophages. Little is known about the human macrophage response to such biomaterials, or the nature of the signaling mechanisms that govern the macrophage phenotype in this environment. The cellular events at the interface of a tissue and implanted decellularized biomaterial were examined by establishing a novel ex vivo tissue culture model in which surgically excised human urinary tract tissue was combined with porcine acellular bladder matrix (PABM). Evaluation of the tissue-biomaterial interface showed a time-dependent infiltration of the biomaterial by CD68(+) CD80(-) macrophages. The migration of CD68(+) cells from the tissue to the interface was accompanied by maturation to a CD163(hi) phenotype, suggesting that factor(s) associated with the biomaterial or the wound edge was/were responsible for the active recruitment and polarization of local macrophages. Glucocorticoid receptor (GR) and peroxisome proliferator activated receptor gamma (PPARγ) signaling was investigated as candidate pathways for integrating inflammatory responses; both showed intense nuclear labeling in interface macrophages. GR and PPARγ activation polarized peripheral blood-derived macrophages from a default M1 (CD80(+)) toward an M2 (CD163(+)) phenotype, but PPARγ signaling predominated, as its antagonism blocked any GR-mediated effect. Seeding on PABM was effective at polarizing peripheral blood-derived macrophages from a default CD80(+) phenotype on glass to a CD80(-) phenotype, with intense nuclear localization of PPARγ. These results endorse in vivo observations that the infiltration of decellularized biological scaffolds, exemplified here by PABM, is pioneered by macrophages. Thus, it appears that natural factors present in PABM are involved in the active recruitment and polarization of macrophages to a CD163(+) phenotype, with activation of PPARγ identified as the candidate pathway. The harnessing of these natural matrix-associated factors may be useful in enhancing the integration of synthetic and other natural biomaterials by polarizing macrophage activation toward an M2 regulatory phenotype

The Epitheliome: agent-based modelling of the social behaviour of cells

We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models

Role of FoxO1 in skeletal muscle metabolism and growth.

There are multiple binding domains on the promoter region of the peroxisome proliferator activator receptor gamma (γ) coactivator-1 α (PGC-1α) gene, including a trio of insulin responsive elements that are activated by the Forkhead box class-O (FoxO1) winged helix transcription factor, which is known to be regulated by acute transforming retrovirus thymoma (Akt). The first two experimental chapters (Chapters 2 and 3) of this thesis indicate that in skeletal muscle biopsy specimens from healthy humans and cultured human skeletal myotubes, insulin phosphorylates Akt (Ser473) and FoxO1 (Thr24, Ser256), leading to reduced nuclear abundance of FoxO1 total protein. This is associated with an insulin-mediated repression of the mRNA expression of PGC-1α and downstream genes associated with oxidative phosphorylation. In contrast, in muscle taken from insulin resistant humans or in palmitate treated insulin resistant myotubes, neither Akt nor FoxO1 was phosphorylated by insulin resulting in a failure for nuclear exclusion of FoxO1 total protein, and an inability for insulin to repress the mRNA expression of PGC-1α and downstream genes. To determine whether the regulation of FoxO1 was Akt dependent, the work that constitutes Chapter 4 describes experiments where Akt2 −/− and wild type mice were treated with or without insulin. Insulin phosphorylated Akt and FoxO1 (Thr24, Ser256) resulted in a reduced nuclear expression of FoxO1 total protein in wild type but not Akt2 −/− skeletal muscle. The mammalian target of rapamycin (mTOR) is regulated by growth factors to promote protein synthesis. In mammalian skeletal muscle, the Forkhead-O1 transcription factor (FoxO1) promotes protein catabolism by activating ubiquitin-protein ligases. Using both C2C12 mouse myoblasts stably expressing FoxO1-ER fusion proteins that are rapidly activated by 4- OH tamoxifen and transgenic mice that specifically overexpress constitutively active FoxO1 in skeletal muscle (FoxO++/+), this work provides evidence that FoxO1 inhibits mTOR signaling and protein synthesis. Activation of constitutively active FoxO1 induced the expression of eukaryotic initiation factor 4E binding protein 1 (eIF4E-BP1) mRNA and protein, but reduced eIF4E-BP1 phosphorylation (Thr37/46). The reduction in eIF4E-BP1 phosphorylation was associated with a reduction in the abundance of Raptor and mTOR, Raptor-associated mTOR, reduced phosphorylation of the downstream protein p70S6 kinase and attenuated protein synthesis. The FoxO++/+ mice, characterized by severe skeletal muscle atrophy, displayed increased nuclear FoxO1 abundance and eIF4E-BP1 protein expression which was associated with reduced eIF4E-BP1 phosphorylation, Raptor, and mTOR protein abundance. These results provide the first evidence that FoxO1 per se inhibits protein synthesis via increased expression of the translational protein eIF4E-BP1 and reduced signaling through mTOR/Raptor complexes. In conclusion, insulin decreases the expression of genes involved in oxidative metabolism in healthy but not insulin resistant muscle, due to a decrease in FoxO1 phosphorylation and nuclear exclusion secondary to reduced Akt activity. FoxO1 may be an important therapeutic target in human disease where catabolism of muscle is observed, as FoxO1 appears to inhibit protein synthesis and translation/initiation pathways

The Impact of Return Migration to Mexico

Hundreds of thousand of Mexicans leave their country each year for the United States. Almost half these migrants return to Mexico within twelve months. Using a sample of working-aged males from (MxFLS) we find that being a return migrant affects the probability of employment. In states along the US border return migrants are less likely to be employed and those in the Central and Capital areas more likely. But these effects disappear when we correct for the fact that factors that determine migration also affect employment.Migration, Mexico, labor outcomes, MxFLS