Temporal difference models describe higher-order learning in humans

The ability to use environmental stimuli to predict impending harm is critical for survival. Such predictions should be available as early as they are reliable. In pavlovian conditioning, chains of successively earlier predictors are studied in terms of higher-order relationships, and have inspired computational theories such as temporal difference learning. However, there is at present no adequate neurobiological account of how this learning occurs. Here, in a functional magnetic resonance imaging (fMRI) study of higher-order aversive conditioning, we describe a key computational strategy that humans use to learn predictions about pain. We show that neural activity in the ventral striatum and the anterior insula displays a marked correspondence to the signals for sequential learning predicted by temporal difference models. This result reveals a flexible aversive learning process ideally suited to the changing and uncertain nature of real-world environments. Taken with existing data on reward learning, our results suggest a critical role for the ventral striatum in integrating complex appetitive and aversive predictions to coordinate behaviour.     

Emergence of cooperation and evolutionary stability in finite populations

To explain the evolution of cooperation by natural selection has been a major goal of biologists since Darwin. Cooperators help others at a cost to themselves, while defectors receive the benefits of altruism without providing any help in return. The standard game dynamical formulation is the 'Prisoner's Dilemma', in which two players have a choice between cooperation and defection. In the repeated game, cooperators using direct reciprocity cannot be exploited by defectors, but it is unclear how such cooperators can arise in the first place. In general, defectors are stable against invasion by cooperators. This understanding is based on traditional concepts of evolutionary stability and dynamics in infinite populations. Here we study evolutionary game dynamics in finite populations. We show that a single cooperator using a strategy like 'tit-for-tat' can invade a population of defectors with a probability that corresponds to a net selective advantage. We specify the conditions required for natural selection to favour the emergence of cooperation and define evolutionary stability in finite populations.     

Iron corrosion by novel anaerobic microorganisms

Corrosion of iron presents a serious economic problem. Whereas aerobic corrosion is a chemical process, anaerobic corrosion is frequently linked to the activity of sulphate-reducing bacteria (SRB). SRB are supposed to act upon iron primarily by produced hydrogen sulphide as a corrosive agent and by consumption of 'cathodic hydrogen' formed on iron in contact with water. Among SRB, Desulfovibrio species--with their capacity to consume hydrogen effectively--are conventionally regarded as the main culprits of anaerobic corrosion; however, the underlying mechanisms are complex and insufficiently understood. Here we describe novel marine, corrosive types of SRB obtained via an isolation approach with metallic iron as the only electron donor. In particular, a Desulfobacterium-like isolate reduced sulphate with metallic iron much faster than conventional hydrogen-scavenging Desulfovibrio species, suggesting that the novel surface-attached cell type obtained electrons from metallic iron in a more direct manner than via free hydrogen. Similarly, a newly isolated Methanobacterium-like archaeon produced methane with iron faster than do known hydrogen-using methanogens, again suggesting a more direct access to electrons from iron than via hydrogen consumption.     

Experimental psychology: event timing turns punishment to reward

Can relief from pain be a pleasure? If so, noxious events should--despite their typically aversive effects--also have a 'rewarding' after-effect. Through training fruitflies by using an electric shock paired with an odour, we show here that the shock can condition either avoidance of this odour or approach to it. These opposing behaviours depend on the relative timing of the shock and odour presentations during training, and indicate that a shock can act as either an aversive reinforcer or an appetitive one.     

Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis

The filamins are cytoplasmic proteins that regulate the structure and activity of the cytoskeleton by cross-linking actin into three-dimensional networks, linking the cell membrane to the cytoskeleton and serving as scaffolds on which intracellular signaling and protein trafficking pathways are organized (reviewed in refs. 1,2). We identified mutations in the gene encoding filamin B in four human skeletal disorders. We found homozygosity or compound heterozygosity with respect to stop-codon mutations in autosomal recessive spondylocarpotarsal syndrome (SCT, OMIM 272460) and missense mutations in individuals with autosomal dominant Larsen syndrome (OMIM 150250) and the perinatal lethal atelosteogenesis I and III phenotypes (AOI, OMIM 108720; AOIII, OMIM 108721). We found that filamin B is expressed in human growth plate chondrocytes and in the developing vertebral bodies in the mouse. These data indicate an unexpected role in vertebral segmentation, joint formation and endochondral ossification for this ubiquitously expressed cytoskeletal protein.     

Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms

Caspases mediate essential key proteolytic events in inflammatory cascades and the apoptotic cell death pathway. Human caspases functionally segregate into two distinct subfamilies: those involved in cytokine maturation (caspase-1, -4 and -5) and those involved in cellular apoptosis (caspase-2, -3, -6, -7, -8, -9 and -10). Although caspase-12 is phylogenetically related to the cytokine maturation caspases, in mice it has been proposed as a mediator of apoptosis induced by endoplasmic reticulum stress including amyloid-beta cytotoxicity, suggesting that it might contribute to the pathogenesis of Alzheimer's disease. Here we show that a single nucleotide polymorphism in caspase-12 in humans results in the synthesis of either a truncated protein (Csp12-S) or a full-length caspase proenzyme (Csp12-L). The read-through single nucleotide polymorphism encoding Csp12-L is confined to populations of African descent and confers hypo-responsiveness to lipopolysaccharide-stimulated cytokine production in ex vivo whole blood, but has no significant effect on apoptotic sensitivity. In a preliminary study, we find that the frequency of the Csp12-L allele is increased in African American individuals with severe sepsis. Thus, Csp12-L attenuates the inflammatory and innate immune response to endotoxins and in doing so may constitute a risk factor for developing sepsis.