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

The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work has recently complemented these studies by identifying dopaminergic neurons in the primate whose fluctuating output apparently signals changes or errors in the predictions of future salient and rewarding events. Taken together, these findings can be understood through quantitative theories of adaptive optimizing control.

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A Neural Substrate of Prediction and Reward

A DNA test to sex most birds.

While the study of psychology has offered little in the way of explaining the creative process, Koestler examines the idea that we are at our most creative when rational thought is suspended--for example, in dreams and trancelike states. All who read The Act of Creation will find it a compelling and illuminating book.

The Act of Creation

Child psychiatrists, pediatricians, and other child clinicians need to have a solid understanding of child language development. There are at least four important reasons that make this necessary. First, slowing, arrest, and deviation of language development are highly associated with, and complicate the course of, child psychopathology. Second, language competence plays a crucial role in emotional and mood regulation, evaluation, and therapy. Third, language deficits are the most frequent underpinning of the learning disorders, ubiquitous in our clinical populations. Fourth, clinicians should not confuse the rich linguistic and dialectal diversity of our clinical populations with abnormalities in child language development. The challenge for the clinician becomes, then, how to get immersed in the captivating field of child language acquisition without getting overwhelmed by its conceptual and empirical complexity. In the past 50 years and since the seminal works of Roger Brown, Jerome Bruner, and Catherine Snow, child language researchers (often known as developmental psycholinguists) have produced a remarkable body of knowledge. Linguists such as Chomsky and philosophers such as Grice have strongly influenced the science of child language. One of the major tenets of Chomskian linguistics (known as generative grammar) is that children’s capacity to acquire language is “hardwired” with “universal grammar”—an innate language acquisition device (LAD), a language “instinct”—at its core. This view is in part supported by the assertion that the linguistic input that children receive is relatively dismal and of poor quality relative to the high quantity and quality of output that they manage to produce after age 2 and that only an advanced, innate capacity to decode and organize linguistic input can enable them to “get from here (prelinguistic infant) to there (linguistic child).” In “Constructing a Language,” Tomasello presents a contrasting theory of how the child acquires language: It is not a universal grammar that allows for language development. Rather, human cognition universals of communicative needs and vocal-auditory processing result in some language universals, such as nouns and verbs as expressions of reference and predication (p. 19). The author proposes that two sets of cognitive skills resulting from biological/phylogenetic adaptations are fundamental to the ontogenetic origins of language. These sets of inherited cognitive skills are intentionreading on the one hand and pattern-finding, on the other. Intention-reading skills encompass the prelinguistic infant’s capacities to share attention to outside events with other persons, establishing joint attentional frames, to understand other people’s communicative intentions, and to imitate the adult’s communicative intentions (an intersubjective form of imitation that requires symbolic understanding and perspective-taking). Pattern-finding skills include the ability of infants as young as 7 months old to analyze concepts and percepts (most relevant here, auditory or speech percepts) and create concrete or abstract categories that contain analogous items. Tomasello, a most prominent developmental scientist with research foci on child language acquisition and on social cognition and social learning in children and primates, succinctly and clearly introduces the major points of his theory and his views on the origins of language in the initial chapters. In subsequent chapters, he delves into the details by covering most language acquisition domains, namely, word (lexical) learning, syntax, and morphology and conversation, narrative, and extended discourse. Although one of the remaining domains (pragmatics) is at the core of his theory and permeates the text throughout, the relative paucity of passages explicitly devoted to discussing acquisition and proBOOK REVIEWS

Constructing a language: A usage-based theory of language acquisition

Vocal learning is a rare trait. Humans depend on vocal learning to acquire spoken language, but most species that communicate acoustically have an innate repertoire of sounds that they use for information exchange. Among the few non-human species that also rely on vocal learning, songbirds have provided by far the most information for understanding this process. This article concentrates on the genetic components of vocal learning in humans and birds. We summarize the existing evidence for a genetic predisposition towards acquiring the species-specific human and avian vocal repertoires. We describe the approaches used for finding genes involved in shaping the neural circuitry required for vocal learning or in mediating the learning process itself. Special attention is given to a particular gene, FOXP2, which has been implicated in a human speech and language disorder. We have studied FoxP2 in avian vocal learners and non-learners and review evidence that links both the molecule and its close homologue FoxP1 to the development of brain regions implicated in vocal learning and to their function. FoxP2 has a characteristic expression pattern in a brain structure uniquely associated with learned vocal communication, Area X in songbirds, or its analogue in parrots and hummingbirds. In both avian song learners and non-learners FoxP2 expression predominates in sensory and sensory-motor circuits. These latter regions also express FoxP2 in mammals and reptiles. We conclude that FoxP2 is important for the building and function of brain pathways including, but not limited to, those essential for learned vocal communication.

Genetic components of vocal learning.

Neurogenetics of birdsong

Signals used in communication often change throughout an individual’s life course. For example, in many song bird species, males modify their song especially between their first and second breeding season. To address one possible reason of such modification, we investigated whether common nightingales Luscinia megarhynchos adjust their song type repertoires to sing the song types commonly occurring in their breeding population. We analysed nocturnal singing of six nightingales in their first and second breeding season and compared their repertoire composition and usage to the ‘typical’ repertoire and usage on the breeding ground (represented by seven reference birds). Songs that were maintained between the first and second season by the six focal birds occurred in most of the repertoires of the seven reference birds and were sung often. In contrast, song types that were dropped from the repertoires occurred less often in the reference birds’ repertoires and were sung less often. Furthermore, in the first year, each focal nightingale’s repertoire was less similar to the reference birds’ repertoires than in the second year. Thus, nightingales adjusted their singing towards the songs popular in the breeding grounds by keeping song types that were common and frequently sung by other individuals in their breeding area and by disposing of infrequently performed ones. This resulted in increased similarity with the population’s repertoire from the first to the second year. We discuss possible ontogenetic processes that may lead to such an adjustment and suggest an improved ability to match song types as possible adaptive value.

Singing the Popular Songs? Nightingales Share More Song Types with Their Breeding Population in Their Second Season than in Their First

Many experiments require early determination of offspring's sex as well as early marking of newborns for individual recognition. According to animal welfare guidelines, non-invasive techniques should be preferred whenever applicable. In our group, we work on different species of song birds in the lab and in the field, and we successfully apply non-invasive methods to sex and individually mark chicks. This paper presents a comprehensive non-invasive tool-box. Sexing birds prior to the expression of secondary sexual traits requires the collection of DNA-bearing material for PCR. We established a quick and easy method to sex birds of any age (post hatching) by extracting DNA from buccal swabs. Results can be obtained within 3 hours. For individual marking chick's down feathers are trimmed in specific patterns allowing fast identification within the hatching order. This set of methods is easily applicable in a standard equipped lab and especially suitable for working in the field as no special equipment is required for sampling and storage. Handling of chicks is minimized and marking and sexing techniques are non-invasive thereby supporting the RRR-principle of animal welfare guidelines.

Who is who? Non-invasive methods to individually sex and mark altricial chicks.

Background 
Mutations in the transcription factor GLI3, a downstream target of Sonic Hedgehog (SHH) signaling, are responsible for the development of malformation syndromes such as Greig-cephalopolysyndactyly-syndrome (GCPS), or Pallister-Hall-syndrome (PHS) Mutations that lead to loss of function of the protein and to haploinsufficiency cause GCPS, while truncating mutations that result in constitutive repressor function of GLI3 lead to PHS As an exception, some point mutations in the C-terminal part of GLI3 observed in GCPS patients have so far not been linked to loss of function We have shown recently that protein phosphatase 2A (PP2A) regulates the nuclear localization and transcriptional activity a of GLI3 function
Principal Findings 
We have shown recently that protein phosphatase 2A (PP2A) and the ubiquitin ligase MID1 regulate the nuclear localization and transcriptional activity of GLI3 Here we show mapping of the functional interaction between the MID1-α4-PP2A complex and GLI3 to a region between amino acid 568-1100 of GLI3 Furthermore we demonstrate that GCPS-associated point mutations, that are located in that region, lead to misregulation of the nuclear GLI3-localization and transcriptional activity GLI3 phosphorylation itself however appears independent of its localization and remains untouched by either of the point mutations and by PP2A-activity, which suggests involvement of an as yet unknown GLI3 interaction partner, the phosphorylation status of which is regulated by PP2A activity, in the control of GLI3 subcellular localization and activity
Conclusions 
The present findings provide an explanation for the pathogenesis of GCPS in patients carrying C-terminal point mutations, and close the gap in our understanding of how GLI3-genotypes give rise to particular phenotypes Furthermore, they provide a molecular explanation for the phenotypic overlap between Opitz syndrome patients with dysregulated PP2A-activity and syndromes caused by GLI3-mutations

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Constance Scharff

Papers

Genetic components of vocal learning.

Neurogenetics of birdsong

Singing the Popular Songs? Nightingales Share More Song Types with Their Breeding Population in Their Second Season than in Their First

Who is who? Non-invasive methods to individually sex and mark altricial chicks.

Point Mutations in GLI3 Lead to Misregulation of its Subcellular Localization