The handaxe and the microscope: individual and social learning in a multidimensional model of adaptation

When individuals learn by trial-and-error, they perform randomly chosen actions and then reinforce those actions that led to a high payoff. However, individuals do not always have to physically perform an action in order to evaluate its consequences. Rather, they may be able to mentally simulate actions and their consequences without actually performing them. Such fictitious learners can select actions with high payoffs without making long chains of trial-and-error learning. Here, we analyze the evolution of an n-dimensional cultural trait (or artifact) by learning, in a payoff landscape with a single optimum. We derive the stochastic learning dynamics of the distance to the optimum in trait space when choice between alternative artifacts follows the standard logit choice rule. We show that for both trial-and-error and fictitious learners, the learning dynamics stabilize at an approximate distance of root n/(2 lambda(e)) away from the optimum, where lambda(e) is an effective learning performance parameter depending on the learning rule under scrutiny. Individual learners are thus unlikely to reach the optimum when traits are complex (n large), and so face a barrier to further improvement of the artifact. We show, however, that this barrier can be significantly reduced in a large population of learners performing payoff-biased social learning, in which case lambda(e) becomes proportional to population size. Overall, our results illustrate the effects of errors in learning, levels of cognition, and population size for the evolution of complex cultural traits. (C) 2013 Elsevier Inc. All rights reserved.

Peptide-antibody conjugates for tumour therapy: a MHC-class-II-restricted tetanus toxin peptide coupled to an anti-Ig light chain antibody can induce cytotoxic lysis of a human B-cell lymphoma by specific CD4 T cells.

Anti-idiotype antibody therapy of B-cell lymphomas, despite numerous promising experimental and clinical studies, has so far met with limited success. Tailor-made monoclonal anti-idiotype antibodies have been injected into a large series of lymphoma patients, with a few impressive complete tumour remissions but a large majority of negative responses. The results presented here suggest that, by coupling to antilymphoma idiotype antibodies a few molecules of the tetanus toxin universal epitope peptide P2 (830-843), one could markedly increase the efficiency of this therapy. We show that after 2-hr incubation with conjugates consisting of the tetanus toxin peptide P2 coupled by an S-S bridge to monoclonal antibodies directed to the lambda light chain of human immunoglobulin, human B-lymphoma cells can be specifically lysed by a CD4 T-lymphocyte clone specific for the P2 peptide. Antibody without peptide did not induce B-cell killing by the CD4 T-lymphocyte clone. The free cysteine-peptide was also able to induce lysis of the B-lymphoma target by the T-lymphocyte clone, but at a molar concentration 500 to 1000 times higher than that of the coupled peptide. Proliferation assays confirmed that the antibody-peptide conjugate was antigenically active at a much lower concentration than the free peptide. They also showed that antibody-peptide conjugates required an intact processing function of the B cell for peptide presentation, which could be selectively inhibited by leupeptin and chloroquine.(ABSTRACT TRUNCATED AT 250 WORDS)

Blue light activates a specific protein kinase in higher plants.

Blue light mediates the phosphorylation of a membrane protein in seedlings from several plant species. When crude microsomal membrane proteins from dark-grown pea (Pisum sativum L.), sunflower (Helianthus annuus L.), zucchini (Cucurbita pepo L.), Arabidopsis (Arabidopsis thaliana L.), or tomato (Lycopersicon esculentum L.) stem segments, or from maize (Zea mays L.), barley (Hordeum vulgare L.), oat (Avena sativa L.), wheat (Triticum aestivum L.), or sorghum (Sorghum bicolor L.) coleoptiles are illuminated and incubated in vitro with [gamma-(32)P]ATP, a protein of apparent molecular mass from 114 to 130 kD is rapidly phosphorylated. Hence, this system is probably ubiquitous in higher plants. Solubilized maize membranes exposed to blue light and added to unirradiated solubilized maize membranes show a higher level of phosphorylation of the light-affected protein than irradiated membrane proteins alone, suggesting that an unirradiated substrate is phosphorylated by a light-activated kinase. This finding is further demonstrated with membrane proteins from two different species, where the phosphorylated proteins are of different sizes and, hence, unambiguously distinguishable on gel electrophoresis. When solubilized membrane proteins from one species are irradiated and added to unirradiated membrane proteins from another species, the unirradiated protein becomes phosphorylated. These experiments indicate that the irradiated fraction can store the light signal for subsequent phosphorylation in the dark. They also support the hypothesis that light activates a specific kinase and that the systems share a close functional homology among different higher plants.

Effect of the TAT-RasGAP(317-326) peptide on apoptosis of human malignant mesothelioma cells and fibroblasts exposed to meso-tetra-hydroxyphenyl-chlorin and light.

BACKGROUND: 5,10,15,20-Tetrakis(m-hydroxyphenyl)chlorin (mTHPC)-mediated photodynamic therapy (PDT) has shown insufficient tumor selectivity for the treatment of pleural mesothelioma. Tumor selectivity of mTHPC-PDT may be enhanced in the presence of the TAT-RasGAP(317-326) peptide which has the potential to specifically sensitize tumor cells to cytostatic agents. MATERIALS AND METHODS: H-meso-1 and human fibroblast cell cultures, respectively, were exposed to two different mTHPC doses followed by light delivery with and without TAT-RasGAP(317-326) administration. mTHPC was added to the cultures at a concentration of 0.04microg/ml and 0.10microg/ml, respectively, 24h before laser light illumination at 652nm (3J/cm(2), 40mW/cm(2)). TAT-RasGAP(317-326) was added to the cultures immediately after light delivery at a concentration of 20microM. The apoptosis rate was determined by scoring the cells displaying pycnotic nuclei. Cell viability was measured by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: Light delivery associated with 0.04microg/ml mTHPC resulted in a significantly higher apoptosis rate in the presence of TAT-RasGAP(317-326) than without in H-meso-1 cells (p<0.05) but not in fibroblasts. In contrast, 1.0microg/ml mTHPC and light resulted in a significantly higher apoptosis rate in both H-meso-1 cells and fibroblasts as compared to controls (p<0.05) but the addition of TAT-RasGAP(317-326) did not lead to a further significant increase of the apoptosis rate of both H-meso-1 cells and fibroblasts as compared to mTHPC and light delivery alone. CONCLUSION: TAT-RasGAP(317-326) selectively enhanced the effect of mTHPC and light delivery on H-meso-1 cells but not on fibroblasts. However, this effect was mTHPC dose-dependent and occurred only at a low sensitizer dose.

Survival and early seedling growth of conifers with different shade tolerance in a Sitka spruce spacing trial and relationship to understorey light climate

Abstract

Nutrient and light availability to white spruce seedlings in partial and clearcut harvested aspen stands

Abstract

Glucocorticoid-induced tumor necrosis factor receptor is a p21Cip1/WAF1 transcriptional target conferring resistance of keratinocytes to UV light-induced apoptosis.

Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a member of the tumor necrosis factor receptor superfamily, is expressed in T lymphocytes, and exerts an anti-apoptotic function in these cells. We reported that GITR is also highly expressed in the skin, specifically in keratinocytes, and that it is under negative transcriptional control of p21(Cip1/WAF1), independently from the cell cycle. Although GITR expression is higher in p21-deficient keratinocytes and skin, it is down-modulated with differentiation and in response to UVB. The combined analysis of keratinocytes with increased GITR expression versus normal keratinocytes and skin of mice with a disruption of the GITR gene indicates that this protein protects keratinocytes from UVB-induced apoptosis both in vitro and in vivo.

Cross-Cultural Adaptation and Validation of the Spinal Function Sort (SFS) for French- and German-Speaking Patients with Back Complaints

Aim: Functional subjective evaluation through questionnaire is fundamental, but not often realized in patients with back complaints, notably because of lack of validated tools, in accordance with recognized psychometric criteria. The Spinal Function Sort (SFS), developed according to actual standards, was only validated in English. The aim of this study is to translate, adapt and validate the French and German version of the SFS.Method and material: The translation and cross-cultural adaptation were performed following the methodology proposed by the American Association of Orthopedist Surgeon. A total of 344 patients, presenting varied back complaints (especially degenerative and traumatic), took part in this study in a tertiary French- (n=87; mean age 44y; 17 women) and German-speaking (n=257; mean age 41y; 53 women) center. Test-retest reliability was quantified using the intraclass correlation coefficient (ICC) and construct validity was assessed by estimating the Pearson's correlation with the SF-36 physical and mental scales, the Visual Analogue Scale for Pain Intensity (VAS), and subscales of the Hospital Anxiety and Depression Scale (HADS).Results: Respectively for the French and German version, ICC were 0.98 and 0.94. Correlations 0.63 and 0.67 with the SF-36 Physical Functioning subscale; 0.60 and 0.52 with the SF-36 Physical Summary Scale ; -0.33 and -0.51 with the VAS ; -0.08 and 0.25 with the SF-36 Mental Health scale; 0.01 and 0.28 with the SF-36 Mental Summary Scale; -0.26 and -0.42 with the HADS depression; -0.17 and -0.45 with the HADS anxiety.Discussion: For both the French and German version of the SFS, the reliability was excellent. Convergent construct validity with SF-36 physical scales is good, moderated with the VAS. We find out a low correlation with SF-36 mental scales (divergent construct validity). We find out a low correlation with HADS subscales in the French version, and a moderate one in the German version. Selection bias, chronicity of the complaints, as well as cultural differences could explain these results. In conclusion, both the French and German version of the SFS are valid and reliable for evaluation of perceived functional capacity for patients with back complaints.

Susceptibility and adaptation to human TRIM5α alleles at positive selected sites in HIV-1 capsid.

Numerous in vitro studies attribute to human TRIM5α some modest anti-HIV-1 activity and human population studies suggest some differential effect of TRIM5α polymorphisms on disease progression. If the activity of TRIM5α were relevant in vivo, it could result in positive selection on the viral capsid. To address this issue, we identified 10 positively selected sites in HIV-1 capsid from multiple viral strains and generated 17 clade B viruses carrying a minor (i.e. low frequency) residue or an alanine at those positions. All recombinant viruses were susceptible to the modest effect of common human TRIM5α and allelic variants R136Q, and H419Y; H43Y and G249D TRIM5α were generally inactive. Increased sensitivity to TRIM5α was observed for some capsid variants, suggesting that minor residues are selected against in human populations. On the other hand, the modest potency of human TRIM5α does not translate in escape mutations in the viral capsid.

Score light

Award-winning

Local adaptation maintains clinal variation in melanin-based coloration of European barn owls (Tyto alba).

Ecological parameters vary in space, and the resulting heterogeneity of selective forces can drive adaptive population divergence. Clinal variation represents a classical model to study the interplay of gene flow and selection in the dynamics of this local adaptation process. Although geographic variation in phenotypic traits in discrete populations could be remainders of past adaptation, maintenance of adaptive clinal variation requires recurrent selection. Clinal variation in genetically determined traits is generally attributed to adaptation of different genotypes to local conditions along an environmental gradient, although it can as well arise from neutral processes. Here, we investigated whether selection accounts for the strong clinal variation observed in a highly heritable pheomelanin-based color trait in the European barn owl by comparing spatial differentiation of color and of neutral genes among populations. Barn owl's coloration varies continuously from white in southwestern Europe to reddish-brown in northeastern Europe. A very low differentiation at neutral genetic markers suggests that substantial gene flow occurs among populations. The persistence of pronounced color differentiation despite this strong gene flow is consistent with the hypothesis that selection is the primary force maintaining color variation among European populations. Therefore, the color cline is most likely the result of local adaptation.