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

Function in the human connectome: Task-fMRI and individual differences in behavior

The aim of the present review article is to guide the reader through portions of the human time perception, or temporal processing, literature. After distinguishing the main contemporary issues related to time perception, the article focuses on the main findings and explanations that are available in the literature on explicit judgments about temporal intervals. The review emphasizes studies that are concerned with the processing of intervals lasting a few milliseconds to several seconds and covers studies issuing from either a behavioral or a neuroscience approach. It also discusses the question of whether there is an internal clock (pacemaker counter or oscillator device) that is dedicated to temporal processing and reports the main hypotheses regarding the involvement of biological structures in time perception.

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Timing and time perception: A review of recent behavioral and neuroscience findings and theoretical directions

Suppose someone had to prepare a review article on visual perception, instead of time perception. This individual would probably ask for a series of reviews, with at least one—and probably several—dedicated to color, distance, shape, and motion perception, and maybe to other aspects of visual perception. It would be very difficult to complete the same exercise for time perception since the categories of temporal experiences are not as clearly defined. However, for a reader to understand the scope of a text on time perception, it is essential to develop a representation of what the main research avenues or categories are. The present text should help the reader to grasp the scope of recent literature related to psychological time and time perception. After a brief overview of the various perspectives on what could be meant by psychological time, the review will propose to identify of series of key concepts and empirical findings that should delineate the field of time perception and timing, and will discuss some models of time perception. The article also provides a review of the main recent findings in the field in which a neuroscientific approach to timing is adopted. In this section, the roles of the cerebellum, of the cerebral cortices, and of the basal ganglia in the timing processes are emphasized. Time Perception Beyond the Focus of the Present Review

TUTORIAL REVIEW Timing and time perception: A review of recent behavioral and neuroscience findings and theoretical directions

Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals. 

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Reproducible brain-wide association studies require thousands of individuals

Machine learning-based approaches are now able to examine functional magnetic resonance imaging data in a multivariate manner and extract features predictive of group membership. We applied support vector machine-based classification to resting state functional connectivity data from nicotine-dependent smokers and healthy controls to identify brain-based features predictive of nicotine dependence. By employing a network-centered approach, we observed that within-network functional connectivity measures offered maximal information for predicting smoking status, as opposed to between-network connectivity, or the representativeness of each individual node with respect to its parent network. Further, our analysis suggests that connectivity measures within the executive control and frontoparietal networks are particularly informative in predicting smoking status. Our findings suggest that machine learning-based approaches to classifying resting state functional connectivity data offer a valuable alternative technique to understanding large-scale differences in addiction-related neurobiology.

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Machine learning classification of resting state functional connectivity predicts smoking status.

Neural responses to a repeated stimulus typically diminish, an effect known as repetition suppression. We here demonstrate what appear to be parallel effects of repetition on subjective duration, even when stimuli are presented too rapidly for explicit temporal judgments. When a brief visual stimulus (e.g., a letter, word, object, or face) was serially flashed in different locations, several stimuli appeared to be present simultaneously due to persistence of visionVwe term this the Proliferation Effect. Critically, fewer stimuli were perceived to be simultaneously present when the same stimulus was flashed repeatedly than when a different stimulus was used for each flash, indicating that persistence of vision (and hence subjective duration) shrinks for predictable stimuli. These short-timescale experiments demonstrate that subjective durations are computed at a preconscious and implicit level of processing, thereby changing the temporal interpretation of visual scenes. Further, these findings suggest a new, instant diagnostic test for deficits in repetition suppression, such as those found in schizophrenia.

Brief subjective durations contract with repetition.

BACKGROUND Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression. METHODOLOGY/PRINCIPAL FINDINGS Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials. CONCLUSIONS/SIGNIFICANCE Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

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Subjective duration distortions mirror neural repetition suppression.

Resting state functional connectivity (rsFC) has provided a new and valuable tool for investigating network-level dysfunction in addiction. Following the recent development of a framework of large scale network disruptions, we have been able to arrive at unique insights into craving-related aspects of addiction using rsFC. However, such network-level advancement has thus far eluded our understanding of mesocorticolimbic involvement in addiction. Given the importance of this system in vulnerability and resilience to addiction, understanding mesocorticolimbic dynamics to the same extent could provide critical insights into the disease. To this end, we review here recent studies on addiction that employ rsfC and suggest a new approach, one that combines a novel model for addiction with new experimental techniques as well as participant groups, to accelerate progress in this arena.

Resting state functional connectivity analysis for addiction medicine: From individual loci to complex networks.

Perceived duration is conventionally assumed to correspond with objective duration, but a growing literature suggests a more complex picture. For example, repeated stimuli appear briefer in duration than a novel stimulus of equal physical duration. We suggest that such duration illusions appear to parallel the neural phenomenon of repetition suppression, and we marshal evidence for a new hypothesis: the experience of duration is a signature of the amount of energy expended in representing a stimulus, i.e. the coding efficiency. This novel hypothesis offers a unified explanation for almost a dozen illusions in the literature in which subjective duration is modulated by properties of the stimulus such as size, brightness, motion and rate of flicker.

Vani Pariyadath

Papers

Machine learning classification of resting state functional connectivity predicts smoking status.

Brief subjective durations contract with repetition.

Subjective duration distortions mirror neural repetition suppression.

Resting state functional connectivity analysis for addiction medicine: From individual loci to complex networks.

Is Subjective Duration a Signature of Coding Efficiency