抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Thirty years of brain imaging research has converged to define the brain’s default network—a novel and only recently appreciated brain system that participates in internal modes of cognition Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations These two subsystems converge on important nodes of integration including the posterior cingulate cortex The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer’s disease

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The Brain's Default Network Anatomy, Function, and Relevance to Disease

Does the autistic child have a theory of mind

Abstract We use a new model of metarepresentational development to predict a cognitive deficit which could explain a crucial component of the social impairment in childhood autism. One of the manifestations of a basic metarepresentational capacity is a ‘theory of mind’. We have reason to believe that autistic children lack such a ‘theory’. If this were so, then they would be unable to impute beliefs to others and to predict their behaviour. This hypothesis was tested using Wimmer and Perner's puppet play paradigm. Normal children and those with Down's syndrome were used as controls for a group of autistic children. Even though the mental age of the autistic children was higher than that of the controls, they alone failed to impute beliefs to others. Thus the dysfunction we have postulated and demonstrated is independent of mental retardation and specific to autism.

Does the Autistic Child Have a''Theory of Mind''? Cognition

Prior to the twentieth century, theories of knowledge were inherently perceptual. Since then, developments in logic, statis- tics, and programming languages have inspired amodal theories that rest on principles fundamentally different from those underlying perception. In addition, perceptual approaches have become widely viewed as untenable because they are assumed to implement record- ing systems, not conceptual systems. A perceptual theory of knowledge is developed here in the context of current cognitive science and neuroscience. During perceptual experience, association areas in the brain capture bottom-up patterns of activation in sensory-motor areas. Later, in a top-down manner, association areas partially reactivate sensory-motor areas to implement perceptual symbols. The stor- age and reactivation of perceptual symbols operates at the level of perceptual components - not at the level of holistic perceptual expe- riences. Through the use of selective attention, schematic representations of perceptual components are extracted from experience and stored in memory (e.g., individual memories of green, purr, hot). As memories of the same component become organized around a com- mon frame, they implement a simulator that produces limitless simulations of the component (e.g., simulations of purr). Not only do such simulators develop for aspects of sensory experience, they also develop for aspects of proprioception (e.g., lift, run) and introspec- tion (e.g., compare, memory, happy, hungry). Once established, these simulators implement a basic conceptual system that represents types, supports categorization, and produces categorical inferences. These simulators further support productivity, propositions, and ab- stract concepts, thereby implementing a fully functional conceptual system. Productivity results from integrating simulators combinato- rially and recursively to produce complex simulations. Propositions result from binding simulators to perceived individuals to represent type-token relations. Abstract concepts are grounded in complex simulations of combined physical and introspective events. Thus, a per- ceptual theory of knowledge can implement a fully functional conceptual system while avoiding problems associated with amodal sym- bol systems. Implications for cognition, neuroscience, evolution, development, and artificial intelligence are explored.

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Perceptual symbol systems.

Beliefs about beliefs: representation and constraining function of wrong beliefs in young children's understanding of deception.

The hypothesis, that a conceptual limitation underlies 3-year-olds' difficulty with false-belief attribution (Wimmer & Perner, 1983), was tested against three competing hypotheses. These were: (1) failure to retain essential facts, (2) failure to understand the normal expectations which give rise to false belief and (3) pragmatic misinterpretation of the test question. Results showed that false-belief attribution remained difficult for younger 3-year-olds despite their retention of essential facts and despite attempts to make expectations more explicit and prevent pragmatic misinterpretation. These findings strengthen the original hypothesis, specified here as the inability to assign conflicting truth values to propositions. This hypothesis can explain why 3-year-olds find pretend play, the distinction between expected and achieved outcomes, the real-imaginary distinction and level 1 perspective taking easier to understand than false belief, the reality-appearance distinction and level 2 perspective taking.

Three-year-olds' difficulty with false belief: The case for a conceptual deficit

“John thinks that Mary thinks that…” attribution of second-order beliefs by 5- to 10-year-old children ☆

The present study assessed reading difficulties and cognitive impairments of German-speaking dyslexic children at grade levels 2, 3, and 4. It was found that German dyslexic children suffered from a pervasive speed deficit for all types of reading tasks, including text, high frequency words, and pseudowords, but at the same time showed generally rather high reading accuracy. For pseudowords, reading refusals or word responses were absent, and the majority of errors was close to the target pronunciation. Reading speed seemed to be most impaired for pseudowords and function words that did not allow the children to take a short-cut from phonemically mediated word processing. The discussion offers a developmental framework for the interpretation of these reading difficulties. For the cognitive tasks, dyslexic children did not differ from age-matched control children on the pseudoword repetition task or the digit span task, indicating that auditory perception and memory were not impaired. On phonological awareness tasks (rhyme oddity detection, vowel substitution, and pseudoword spelling), dyslexic children scored lower than age-matched control children, but not lower than younger reading-level control children. The performance of the dyslexic children on the phonemic segmentation tasks (pseudoword spelling and vowel substitution) was high in absolute terms. In contrast, marked differences between dyslexic and age-matched controls were found on rapid naming tasks: dyslexic grade 4 children showed lower numeral-naming speed than reading-level grade 2 children. Numeral-naming speed turned out to be the most important predictor of reading speed differences. These findings are discussed in relation to the phonological impairment explanation of dyslexia and to recent alternative explanations that posit an underlying impairment in automatizing skills which demand the fast execution of low-level cognitive processes.

Characteristics of developmental dyslexia in a regular writing system

In a longitudinal study, development of word reading fluency and spelling were followed for almost 8 years. In a group of 115 students (65 girls, 50 boys) acquiring the phonologically transparent German orthography, prediction measures (letter knowledge, phonological short-term memory, phonological awareness, rapid automatized naming, and nonverbal IQ) were assessed at the beginning of Grade 1; reading fluency and spelling were tested at the end of Grade 1 as well as in Grades 4 and 8. Reading accuracy was close to ceiling in all reading assessments, such that reading fluency was not heavily influenced by differences in reading accuracy. High stability was observed for word reading fluency development. Of the dysfluent readers in Grade 1, 70% were still poor readers in Grade 8. For spelling, children who at the end of Grade 1 still had problems translating spoken words into phonologically plausible letter sequences developed problems with orthographic spelling later on. The strongest specific predictors were rapid automatized naming for reading fluency and phonological awareness for spelling. Word recognition speed was a relevant and highly stable indicator of reading skills and the only indicator that discriminated reading skill levels in consistent orthographies. Its long-term development was more strongly influenced by early naming speed than by phonological awareness.

Heinz Wimmer

Papers

Beliefs about beliefs: representation and constraining function of wrong beliefs in young children's understanding of deception.

Three-year-olds' difficulty with false belief: The case for a conceptual deficit

“John thinks that Mary thinks that…” attribution of second-order beliefs by 5- to 10-year-old children ☆

Characteristics of developmental dyslexia in a regular writing system

Development of word reading fluency and spelling in a consistent orthography: An 8-year follow-up.