The Evolution of Cooperation in Spatially Heterogeneous Populations

A challenging problem in sociobiology is to understand the emergence of cooperation in a nonsocial world. Recent models of the iterated Prisoner's Dilemma (IPD) game conclude that population mixing due to individual mobility limits cooperation; however, these models represent space only implicitly. Here we develop a dynamical IPD model where temporal and spatial variations in the population are explicitly considered. Our model accounts for the stochastic motion of individuals and the inherent nonrandomness of local interactions. By deriving a spatial version of Hamilton's rule, we find that a threshold level of mobility in selfish always-defect (AD) players is required to beget invasion by social 'tit for tat'(TFT) players. Furthermore, the level of mobility of successful TFT newcomers must be approximately equal to or somewhat higher than that of resident defectors. Significant mobility promotes the assortment of TFT pioneers on the front of invasion and of AD intruders in the core of a cooperative cluster. It also maximizes the likelihood of TFT retaliation. Once this first step whereby TFT takes over AD is completed, more generous and perhaps more suspicious strategies may outperform and displace TFT. We derive the conditions under which this continued evolution of more robust cooperative strategies occurs

Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?

To sustain their malignancy, tumour cells acquire several metabolic adaptations such as increased oxygen, glucose, glutamine, and lipids uptake. Other metabolic processes are also enhanced as part of tumour metabolic reprogramming, for example, increased serine metabolism. Serine is a non-essential amino acid that supports several metabolic processes that are crucial for the growth and survival of proliferating cells, including protein, DNA, and glutathione synthesis. Indeed, increased activity of D-3-phosphoglycerate dehydrogenase (PHGDH), the enzyme rate-limiting de novo serine synthesis, has been extensively reported in several tumours. Therefore, selective inhibition of PHGDH may represent a new therapeutic strategy for over-expressing PHGDH tumours, owing to its downstream inhibition of essential biomass production such as one-carbon units and nucleotides. This perspective article will discuss the current status of research into small molecular inhibitors against PHGDH in colorectal cancer, breast cancer, and Ewing's sarcoma. We will summarise recent studies on the development of PHGDH-inhibitors, highlighting their clinical potential as new therapeutics. It also wants to shed a light on some of the key limitations of the use of PHGDH-inhibitors in cancer treatment which are worth taking into account

The Sigma Profile: A Formal Tool to Study Organization and its Evolution at Multiple Scales

The $\sigma$ profile is presented as a tool to analyze the organization of systems at different scales, and how this organization changes in time. Describing structures at different scales as goal-oriented agents, one can define $\sigma \in [0,1]$ ("satisfaction") as the degree to which the goals of each agent at each scale have been met. $\sigma$ reflects the organization degree at that scale. The $\sigma$ profile of a system shows the satisfaction at different scales, with the possibility to study their dependencies and evolution. It can also be used to extend game theoretic models. A general tendency on the evolution of complexity and cooperation naturally follows from the $\sigma$ profile. Experiments on a virtual ecosystem are used as illustration

Did Human Culture Emerge in a Cultural Evolutionary Transition in Individuality?

Evolutionary Transitions in Individuality (ETI) have been responsible for the major transitions in levels of selection and individuality in natural history, such as the origins of prokaryotic and eukaryotic cells, multicellular organisms, and eusocial insects.\ua0The integrated hierarchical organization of life thereby emerged as groups of individuals repeatedly evolved into new and more complex kinds of individuals. The Social Protocell Hypothesis (SPH) proposes that the integrated hierarchical organization of human culture can also be understood as the outcome of an ETI—one that produced a\ua0“cultural organism” (a “sociont”) from a substrate of socially learned traditions that were contained in growing and dividing social communities. The SPH predicts that a threshold\ua0degree of evolutionary individuality would have been achieved by 2.0–2.5 Mya, followed by an increasing degree of evolutionary individuality as the ETI unfolded. We here assess the SPH by applying a battery of criteria—developed to assess evolutionary individuality in biological units—to cultural units across the evolutionary history of Homo. We find an increasing agreement with these criteria, which buttresses the claim that an ETI occurred in the cultural realm

Filling a gap: initial evidence for reliable and valid measures of students’ self-concept, self-efficacy, and interest in science with elementary students traditionally underrepresented in STEM

American students continue to perform poorly on national and international assessments of Science, Technology, Engineering, and Mathematics (STEM) competencies, and achievement gaps spanning racial/ethnic and socioeconomic lines emerge early and widen over time. Scholars and practitioners agree that expanding access to high-quality STEM education has the potential to improve students’ performance and reduce inequalities. Research has elucidated the critical role that students’ self-perceptions play in driving academic achievement, which has spurred the development of many educational programs and initiatives aimed at increasing students’ confidence, self-efficacy, and interest. However, our capacity to determine what programs and initiatives are effective and for whom is limited by our lack of psychometrically sound measures that assess science-related self-perceptions and interests of elementary students from diverse populations. To address this gap, we developed and tested measures of Science Self-Efficacy, Science Self-Concept, Interest in Science Activities, and Attitudes toward STEM careers in a sample of third-grade students (8–9 years) traditionally underrepresented in STEM careers (94% of our sample identified as either African American or Hispanic). We present initial evidence, from a preliminary pilot study, for the reliability and validity of these measures and reveal the multi-dimensional nature of students’ self-perceptions and interests in science. We discuss how such measurement tools will inform our understanding of the nature of young students’ science self-perceptions, how the utilization of such tools can inform educational practice, and highlight the critical importance of conducting measurement development research with diverse populations

RasGTPase-activating protein is a target of caspases in spontaneous apoptosis of lung carcinoma cells and in response to etoposide

p120 RasGTPase-activating protein (RasGAP), the main regulator of Ras GTPase family members, is cleaved at low caspase activity into an N-terminal fragment that triggers potent anti-apoptotic signals via activation of the Ras/PI-3 kinase/Akt pathway. When caspase activity is increased, RasGAP fragment N is further processed into two fragments that effectively potentiate apoptosis. Expression of RasGAP protein and its cleavage was assessed in human lung cancer cells with different histology and responsiveness to anticancer drug-induced apoptosis. Here we show that therapy-sensitive small lung carcinoma cell (SCLC) lines have lower RasGAP expression levels and higher spontaneous cleavage with formation of fragment N compared to therapy-resistant non-small cell lung carcinoma cell (NSCLC) lines. The first RasGAP cleavage event strongly correlated with the increased level of spontaneous apoptosis in SCLC. However, generation of protective RasGAP fragment N also related to the potency of SCLC to develop secondary therapy-resistance. In response to etoposide (ET), RasGAP fragment N was further cleaved in direct dependence on caspase-3 activity, which was more pronounced in NSCLC cells. Caspase inhibition, while effectively preventing the second cleavage of RasGAP, barely affected the first cleavage of RasGAP into fragment N that was always detectable in NSCLC and SCLC cells. These findings suggest that different levels of RasGAP and fragment N might play a significant role in the biology and different clinical course of both subtypes of lung neoplasms. Furthermore, constitutive formation of RasGAP fragment N can potentially contribute to primary resistance of NSCLC to anticancer therapy by ET but also to secondary therapy-resistance in SCL

Effect of RasGAP N2 Fragment-Derived Peptide on Tumor Growth in Mice

Peptides that interfere with the natural resistance of cancer cells to genotoxin-induced apoptosis may improve the efficacy of anticancer regimens. We have previously reported that a cell-permeable RasGAP-derived peptide (TAT-RasGAP317-326) specifically sensitizes tumor cells to genotoxin-induced apoptosis in vitro. Here, we examined the in vivo stability of a protease-resistant D-form of the peptide, RI·TAT-RasGAP317-326, and its effect on tumor growth in nude mice bearing subcutaneous human colon cancer HCT116 xenograft tumors. After intraperitoneal injection, RI·TAT-RasGAP317-326 persisted in the blood of nude mice for more than 1 hour and was detectable in various tissues and subcutaneous tumors. Tumor-bearing mice treated daily for 7 days with RI·TAT-RasGAP317-326 (1.65 mg/kg body weight) and cisplatin (0.5 mg/kg body weight) or doxorubicin (0.25 mg/kg body weight) displayed reduced tumor growth compared with those treated with either genotoxin alone (n = 5-7 mice per group; P = .004 and P = .005, respectively; repeated measures analysis of variance [ANOVA, two-sided]). This ability of the RI·TAT-RasGAP317-326 peptide to enhance the tumor growth inhibitory effect of cisplatin was still observed at peptide doses that were at least 150-fold lower than the dose lethal to 50% of mice. These findings provide the proof of principle that RI·TAT-RasGAP317-326 may be useful for improving the efficacy of chemotherapy in patient