Money and trust among strangers

What makes money essential for the functioning of modern society? Through an experiment, we present evidence for the existence of a relevant behavioral dimension in addition to the standard theoretical arguments. Subjects faced repeated opportunities to help an anonymous counterpart who changed over time. Cooperation required trusting that help given to a stranger today would be returned by a stranger in the future. Cooperation levels declined when going from small to large groups of strangers, even if monitoring and payoffs from cooperation were invariant to group size. We then introduced intrinsically worthless tokens. Tokens endogenously became money: subjects took to reward help with a token and to demand a token in exchange for help. Subjects trusted that strangers would return help for a token. Cooperation levels remained stable as the groups grew larger. In all conditions, full cooperation was possible through a social norm of decentralized enforcement, without using tokens. This turned out to be especially demanding in large groups. Lack of trust among strangers thus made money behaviorally essential. To explain these results, we developed an evolutionary model. When behavior in society is heterogeneous, cooperation collapses without tokens. In contrast, the use of tokens makes cooperation evolutionarily stable.     

Functional genomic screen of human stem cell differentiation reveals pathways involved in neurodevelopment and neurodegeneration

Human embryonic stem cells (hESCs) can be induced and differentiated to form a relatively homogeneous population of neuronal precursors in vitro. We have used this system to screen for genes necessary for neural lineage development by using a pooled human short hairpin RNA (shRNA) library screen and massively parallel sequencing. We confirmed known genes and identified several unpredicted genes with interrelated functions that were specifically required for the formation or survival of neuronal progenitor cells without interfering with the self-renewal capacity of undifferentiated hESCs. Among these are several genes that have been implicated in various neurodevelopmental disorders (i.e., brain malformations, mental retardation, and autism). Unexpectedly, a set of genes mutated in late-onset neurodegenerative disorders and with roles in the formation of RNA granules were also found to interfere with neuronal progenitor cell formation, suggesting their functional relevance in early neurogenesis. This study advances the feasibility and utility of using pooled shRNA libraries in combination with next-generation sequencing for a high-throughput, unbiased functional genomic screen. Our approach can also be used with patient-specific human-induced pluripotent stem cell-derived neural models to obtain unparalleled insights into developmental and degenerative processes in neurological or neuropsychiatric disorders with monogenic or complex inheritance.     

Economic repercussions of fisheries-induced evolution

Fish stocks experiencing high fishing mortality show a tendency to mature earlier and at a smaller size, which may have a genetic component and therefore long-lasting economic and biological effects. To date, the economic effects of such ecoevolutionary dynamics have not been empirically investigated. Using 70 y of data, we develop a bioeconomic model for Northeast Arctic cod to compare the economic yield in a model in which life-history traits can vary only through phenotypic plasticity with a model in which, in addition, genetic changes can occur. We find that evolutionary changes toward faster growth and earlier maturation occur consistently even if a stock is optimally managed. However, if a stock is managed optimally, the evolutionary changes actually increase economic yield because faster growth and earlier maturation raise the stock’s productivity. The optimal fishing mortality is almost identical for the evolutionary and nonevolutionary model and substantially lower than what it has been historically. Therefore, the costs of ignoring evolution under optimal management regimes are negligible. However, if fishing mortality is as high as it has been historically, evolutionary changes may result in economic losses, but only if the fishery is selecting for medium-sized individuals. Because evolution facilitates growth, the fish are younger and still immature when they are susceptible to getting caught, which outweighs the increase in productivity due to fish spawning at an earlier age.     

BCL11B,FLT3, NOTCH1 and FBXW7 mutation status in T-cell acute lymphoblastic leukemia patients

T‐cell acute lymphoblastic leukemia is a heterogeneous malignancy originating from developing lymphocyte precursors likely due to mutations in genes regulating thymocyte differentiation. Here, we characterized mutation status of BCL11B and FLT3 genes, presumably involved in T-ALL, together with FBXW7 and NOTCH1 as known players in T-ALL in 65 pediatric T-cell acute lymphoblastic leukemia patients. We also aimed at the assessment of prognostic value of NOTCH1 and FBXW7 mutations in ALL-IC BFM 2002 protocol.FLT3 and BCL11B mutations were detected in 3% and 2% of patients, respectively. FBXW7 mutations were observed in 8% of patients, while NOTCH1 was mutated in 40%. No correlation was found between NOTCH1 and FBXW7 mutations and traditionally used clinical factors or molecular features. In total we have detected nine mutations, which have not been previously described by others. Eight of them were found in NOTCH1 and one in BCL11B gene.Observed frequencies of NOTCH1 and FBXW7 are in line with previous reports, thus confirming postulated participation of these two genes in T-ALL pathomechanism. Moreover, we report on mutation frequency of FLT3 and BCL11B, not extensively studied in T-ALL so far. Finally, we suggest a putative role of BLC11B as an oncogene in T-ALL pathogenesis.     

Exercise-Induced Decrease in Myocardial High-Energy Phosphate Metabolites in Patients With Chagas Heart Disease

BackgroundThe influence of exercise on cardiac metabolic response in patients with Chagas disease is incompletely understood.Methods and ResultsChanges in cardiac energetic metabolism were investigated in Chagas disease patients before and during isometric handgrip exercise with ³¹P magnetic resonance spectroscopy (MRS). Twenty-eight patients (10 with systolic dysfunction: group I; 10 with normal systolic function and electrocardiogram (ECG) abnormalities: group II; and 8 asymptomatic without ECG abnormalities: group III) and 8 healthy control subjects (group C) were evaluated by electrocardiogram, echocardiogram, functional tests for coronary artery disease, and image-selected localized cardiac ³¹P-MRS. The myocardial phosphocreatine to [β-phosphate]adenosine triphosphate ratio (PCr/β-ATP) was measured at rest and during isometric handgrip exercise. Exercise testing or 99mTc–sestamibi scintigraphy were negative for myocardial ischemia in all individuals. At rest, cardiac PCr/β-ATP was decreased in all Chagas groups (1.23 ± 0.37) versus group C (1.88 ± 0.08; P < .001) and was lower in group I (0.89 ± 0.24) versus groups II (1.44 ± 0.23) and III (1.40 ± 0.37; P < .001). There was no stress-induced change in cardiac PCr/β-ATP (1.88 ± 0.08 at rest vs 1.89 ± 0.08 during exercise; P = NS) in group C. Mean cardiac PCr/β-ATP was 0.89 ± 0.24 and 0.56 ± 0.21 at rest and during exercise, respectively, in group I (37% decrease; P < .001). In group II, PCr/β-ATP was 1.44 ± 0.23 at rest and 0.97 ± 0.37 during exercise (33% decrease; P < .001). In group III, PCr/β-ATP was 1.40 ± 0.37 at rest and 0.60 ± 0.19 during exercise (57% decrease; P < .001).ConclusionsMyocardial high-energy phosphates are reduced at rest in Chagas heart disease patients, and the reduction is greater in patients with left ventricular dysfunction. Regardless of left ventricular function, Chagas patients exhibit an exercise-induced decline in cardiac high-energy phosphates consistent with myocardial ischemia, suggesting the possibility that this metabolic approach may offer a tool to probe new interventions in Chagas disease patients.