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JournalISSN: 0960-9822

Current Biology 

About: Current Biology is an academic journal. The journal publishes majorly in the area(s): Population & Mitosis. It has an ISSN identifier of 0960-9822. Over the lifetime, 18086 publication(s) have been published receiving 1286066 citation(s). The journal is also known as: Curr. Biol..

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TL;DR: For example, Frith as discussed by the authors showed that children with autism have a specific problem with theory-of-mind tasks, such as looking for the hidden chocolate in the cupboard.
Abstract: What is ‘theory of mind’? Maxi eats half his chocolate bar and puts the rest away in the kitchen cupboard. Then he goes out to play in the sun. Meanwhile Maxi’s mother comes into the kitchen, opens the cupboard and sees the chocolate bar. She puts it in the fridge. When Maxi comes back into the kitchen, where will he look for his chocolate bar? The answer to this question will seem obvious. First, Maxi doesn’t know that his mother has moved the chocolate. Second, Maxi still believes, falsely, that his chocolate is in the cupboard. That is why he looks in the cupboard. If this is how you answered the question then you have a ‘theory of mind’. We naturally explain people’s behavior on the basis of their minds: their knowledge, their beliefs and their desires, and we know that when there is a conflict between belief and reality it is the persons’ belief, not the reality that will determine their behavior. Explaining behavior in this way is called ‘having a theory of mind’ or ‘having an intentional stance.’Where will Maxi look for his chocolate? (From the collection of Uta Frith.)View Large Image | View Hi-Res Image | Download PowerPoint SlideWhat is the advantage of having a theory of mind? Through having a theory of mind we can recognize that another person’s knowledge is different from our own. I know what’s behind the rock, but he doesn’t, because, from where he is, he cannot see that there is a scorpion. Having a theory of mind allows us to manipulate other people’s behavior by manipulating their beliefs. If he is my friend I can warn him about the scorpion. If he is my enemy I can tell him it is safe. This latter is called tactical deception or Machiavellianism. Human interactions predominantly involve the dissemination of true or false knowledge for good or for ill.Who has a theory of mind? Up to the age of about five years, a child told the story of Maxi and his mother will say confidently that Maxi will look for his chocolate in the fridge. It is as if they assumed that what they know to be true everyone else knows too. Nevertheless, even three-year-olds look first at the cupboard when the question is asked, and even 15-month-olds can be shown to have an inkling of what is going on; their eye gaze pattern shows that they are surprised if Maxi looks in the fridge. But only from age five or so do children show full understanding of the situation and become able to explain exactly why Maxi has a false belief.Children with autism have a specific problem with theory of mind tasks. They expect Maxi to look for his chocolate in the fridge. They reach a mental age of about 10 years before they achieve an understanding of the Maxi task. More complex problems that involve white lies or double bluff take them even longer to learn, and they may never grasp them fully. Theory of mind difficulties can also be acquired through brain damage in frontal cortex or in the region of the temporo-parietal junction.From field studies there are accounts of a range of animals using tactical deception. But there is still argument over whether even chimpanzees show evidence of this in controlled experiments. The current view is that chimpanzees may have a rudimentary theory of mind, but monkeys (and other animals) probably do not.What is so important about deception and false belief in the study of theory of mind? Having a theory of mind enables many important human interactions other than deception, in particular teaching. But deception is important in the study of theory of mind because of its association with false beliefs. If Maxi’s belief about his chocolate were true — it was still in the cupboard — then you can correctly report where Maxi will look either by basing this prediction on what Maxi believes (because you have a theory of mind) or by basing this prediction on where the chocolate really is (not requiring having a theory of mind). Thus, when successfully solving false belief tasks, where there is a conflict between the false belief and the true state of affairs, we can deduce that theory of mind is engaged.How is theory of mind possible? In order to explain people’s behavior on the basis of their minds, we need to have some idea of what is in their minds. The ability to acquire knowledge about other peoples’ beliefs and desires is called ‘mentalizing’ or ‘mind reading’. Our understanding of the mechanisms underlying this ability remains rudimentary. In everyday speech we frequently explain behavior in terms of mental states. Maxi will look in the cupboard because that’s where he believes his chocolate is and because he wants to eat it. Maxi doesn’t know the chocolate is in the fridge. These everyday explanations of behavior in terms of mental states are referred to as folk psychology. Perhaps our ability to mentalize depends upon representations within the brain of the propositions that make up this theory of behavior (referred to as theory theory). On the other hand, perhaps the ability to mentalize is related to our capacity to empathize with other people: to put ourselves into their shoes (this is referred to as simulation theory).An influential view is that mentalizing crucially depends on the ability to form meta-representations, that is, representations that are decoupled from reality. Thus the truth of the statement, ‘Maxi believes his chocolate is in the cupboard’ does not depend upon where the chocolate is in reality. A possible starting point for developing a mechanistic account of mentalizing comes from the problem of perspective taking. The computation of what another person sees from a different point of view than yours involves translation between egocentric and allocentric spatial co-ordinates. This translation is also fundamental in spatial navigation. It is perhaps no coincidence that in young children the ability to solve spatial viewpoint problems emerges at about the same age as the ability to solve false belief tasks.What is the neural basis of mind reading? There is currently much interest in identifying a social brain: a circumscribed network of brain regions specialized for the social domain. Mentalizing is one of a number of problems confronting this social brain. When brain activity is measured during the performance of a wide range of tasks engaging theory of mind, two regions have been consistently identified: a medial prefrontal region (paracingulate cortex) and the temporo-parietal junction in the superior temporal sulcus.The medial frontal region is also engaged when subjects reflect upon their own mental states, as well as those of others with the more inferior orbital region responding especially to emotional states. The temporo-parietal junction, on the other hand, seems to have a special role in using perceptual cues to recognize the actions and intentions of biological agents. Identification of the precise role of these regions awaits the development of a mechanistic account of our remarkable ability to make inferences about the minds of others.

3,185 citations

Journal ArticleDOI
TL;DR: 34 novel miRNAs were identified by tissue-specific cloning of approximately 21-nucleotide RNAs from mouse and a miRNA was identified that appears to be the fruitfly and mammalian ortholog of C. elegans lin-4 stRNA.
Abstract: MicroRNAs (miRNAs) are a new class of noncoding RNAs, which are encoded as short inverted repeats in the genomes of invertebrates and vertebrates [1, 2]. It is believed that miRNAs are modulators of target mRNA translation and stability, although most target mRNAs remain to be identified. Here we describe the identification of 34 novel miRNAs by tissue-specific cloning of approximately 21-nucleotide RNAs from mouse. Almost all identified miRNAs are conserved in the human genome and are also frequently found in nonmammalian vertebrate genomes, such as pufferfish. In heart, liver, or brain, it is found that a single, tissue-specifically expressed miRNA dominates the population of expressed miRNAs and suggests a role for these miRNAs in tissue specification or cell lineage decisions. Finally, a miRNA was identified that appears to be the fruitfly and mammalian ortholog of C. elegans lin-4 stRNA.

3,177 citations

Journal ArticleDOI
TL;DR: It is argued that redox biology, rather than oxidative stress, underlies physiological and pathological conditions.
Abstract: Oxidative stress refers to elevated intracellular levels of reactive oxygen species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress has been linked to a myriad of pathologies. However, elevated ROS also act as signaling molecules in the maintenance of physiological functions — a process termed redox biology. In this review we discuss the two faces of ROS — redox biology and oxidative stress — and their contribution to both physiological and pathological conditions. Redox biology involves a small increase in ROS levels that activates signaling pathways to initiate biological processes, while oxidative stress denotes high levels of ROS that result in damage to DNA, protein or lipids. Thus, the response to ROS displays hormesis, given that the opposite effect is observed at low levels compared with that seen at high levels. Here, we argue that redox biology, rather than oxidative stress, underlies physiological and pathological conditions.

3,108 citations

Journal ArticleDOI
TL;DR: In this paper, a protein kinase that phosphorylates PKB α at Thr308 and increases its activity over 30-fold was found to play a key role in mediating the activation of PKB by insulin and growth factors.
Abstract: Background: Protein kinase B (PKB), also known as c-Akt, is activated rapidly when mammalian cells are stimulated with insulin and growth factors, and much of the current interest in this enzyme stems from the observation that it lies ‘downstream' of phosphoinositide 3-kinase on intracellular signalling pathways. We recently showed that insulin or insulin-like growth factor 1 induce the phosphorylation of PKB at two residues, Thr308 and Ser473. The phosphorylation of both residues is required for maximal activation of PKB. The kinases that phosphorylate PKB are, however, unknown. Results: We have purified 500 000-fold from rabbit skeletal muscle extracts a protein kinase which phosphorylates PKB α at Thr308 and increases its activity over 30-fold. We tested the kinase in the presence of several inositol phospholipids and found that only low micromolar concentrations of the D enantiomers of either phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P 3 ) or PtdIns(3,4)P 2 were effective in potently activating the kinase, which has been named PtdIns(3,4,5)P 3 -dependent protein kinase-1 (PDK1). None of the inositol phospholipids tested activated or inhibited PKB α or induced its phosphorylation under the conditions used. PDK1 activity was not affected by wortmannin, indicating that it is not likely to be a member of the phosphoinositide 3-kinase family. Conclusions: PDK1 is likely to be one of the protein kinases that mediate the activation of PKB by insulin and growth factors. PDK1 may, therefore, play a key role in mediating many of the actions of the second messenger(s) PtdIns(3,4,5)P 3 and/or PtdIns(3,4)P 2 .

2,732 citations

Journal ArticleDOI
TL;DR: It is found that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals.
Abstract: The mammalian TOR (mTOR) pathway integrates nutrient- and growth factor-derived signals to regulate growth, the process whereby cells accumulate mass and increase in size. mTOR is a large protein kinase and the target of rapamycin, an immunosuppressant that also blocks vessel restenosis and has potential anticancer applications. mTOR interacts with the raptor and GbetaL proteins to form a complex that is the target of rapamycin. Here, we demonstrate that mTOR is also part of a distinct complex defined by the novel protein rictor (rapamycin-insensitive companion of mTOR). Rictor shares homology with the previously described pianissimo from D. discoidieum, STE20p from S. pombe, and AVO3p from S. cerevisiae. Interestingly, AVO3p is part of a rapamycin-insensitive TOR complex that does not contain the yeast homolog of raptor and signals to the actin cytoskeleton through PKC1. Consistent with this finding, the rictor-containing mTOR complex contains GbetaL but not raptor and it neither regulates the mTOR effector S6K1 nor is it bound by FKBP12-rapamycin. We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals.

2,442 citations

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