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

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Inferring resting-state connectivity patterns from functional magnetic resonance imaging (fMRI) data is a challenging task for any analytical technique. In this paper, we review a probabilistic independent component analysis (PICA) approach, optimized for the analysis of fMRI data, and discuss the role which this exploratory technique can take in scientific investigations into the structure of these effects. We apply PICA to fMRI data acquired at rest, in order to characterize the spatio-temporal structure of such data, and demonstrate that this is an effective and robust tool for the identification of low-frequency resting-state patterns from data acquired at various different spatial and temporal resolutions. We show that these networks exhibit high spatial consistency across subjects and closely resemble discrete cortical functional networks such as visual cortical areas or sensory-motor cortex.

/pdf/investigations-into-resting-state-connectivity-using-2ztrvae9kb.pdf

Investigations into resting-state connectivity using independent component analysis

The concept of cognitive reserve provides an explanation for differences between individuals in susceptibility to age-related brain changes or pathology related to Alzheimer's disease, whereby some people can tolerate more of these changes than others and maintain function. Epidemiological studies suggest that lifelong experiences, including educational and occupational attainment, and leisure activities in later life, can increase this reserve. For example, the risk of developing Alzheimer's disease is reduced in individuals with higher educational or occupational attainment. Reserve can conveniently be divided into two types: brain reserve, which refers to differences in the brain structure that may increase tolerance to pathology, and cognitive reserve, which refers to differences between individuals in how tasks are performed that might enable some people to be more resilient to brain changes than others. Greater understanding of the concept of cognitive reserve could lead to interventions to slow cognitive ageing or reduce the risk of dementia.

/pdf/cognitive-reserve-in-ageing-and-alzheimer-s-disease-2ksgairnop.pdf

Cognitive reserve in ageing and Alzheimer's disease

Deficits in daytime performance due to sleep loss are experienced universally and associated with a significant social, financial, and human cost. Microsleeps, sleep attacks, and lapses in cognition increase with sleep loss as a function of state instability. Sleep deprivation studies repeatedly show a variable (negative) impact on mood, cognitive performance, and motor function due to an increasing sleep propensity and destabilization of the wake state. Specific neurocognitive domains including executive attention, working memory, and divergent higher cognitive functions are particularly vulnerable to sleep loss. In humans, functional metabolic and neurophysiological studies demonstrate that neural systems involved in executive function (i.e., prefrontal cortex) are more susceptible to sleep deprivation in some individuals than others. Recent chronic partial sleep deprivation experiments, which more closely replicate sleep loss in society, demonstrate that profound neurocognitive deficits accumulate over time in the face of subjective adaptation to the sensation of sleepiness. Sleep deprivation associated with disease-related sleep fragmentation (i.e., sleep apnea and restless legs syndrome) also results in neurocognitive performance decrements similar to those seen in sleep restriction studies. Performance deficits associated with sleep disorders are often viewed as a simple function of disease severity; however, recent experiments suggest that individual vulnerability to sleep loss may play a more critical role than previously thought.

/pdf/neurocognitive-consequences-of-sleep-deprivation-hg8oxdvlng.pdf

Neurocognitive Consequences of Sleep Deprivation

Dysfunction of the basal ganglia and the brain nuclei interconnected with them leads to disturbances of movement and cognition, including disordered timing of movement and perceptual timing deficits. Patients with Parkinson's disease (PD) were studied in temporal reproduction tasks. We examined PD patients when brain dopamine (DA) transmission was impaired (OFF state) and when DA transmission was reestablished, at the time of maximal clinical benefit following administration of levodopa + apomorphine (ON state). Patients reproduced target times of 8 and 21 sec trained in blocked trials with the peak interval procedure, which were veridical in the ON state, comparable to normative performance by healthy young and aged controls (Experiment 1). In the OFF state, temporal reproduction was impaired in both accuracy and precision (variance). The 8-sec signal was reproduced as longer and the 21-sec signal was reproduced as shorter than they actually were (Experiment 1). This ''migration'' effect was dependent upon training of two different durations. When PD patients were trained on 21 sec only (Experiment 2), they showed a reproduction error in the long direction, opposite to the error produced under the dual training condition of Experiment 1. The results are discussed as a mutual attraction between temporal processing systems, in memory and clock stages, when dopaminergic regulation in the striatum is dysfunctional.

Coupled Temporal Memories in Parkinson's Disease: A Dopamine-Related Dysfunction

The properties of the internal clock, temporal memory, and decision processes used to time short durations were investigated. The peak-interval procedure was used to evaluate the timing of 8-, 12-, and 21-s intervals, and analyses were conducted on the mean response functions and on individual trials. A distractor task prevented counting, and visual feedback on accuracy and precision was provided after each trial. Mean response distributions were (a) centered at the appropriate real-time criteria, (b) highly symmetrical, and (c) scalar in their variability. Analysis of individual trials indicated more memory variability relative to response threshold variability. Taken together, these results demonstrate that humans show the same qualitative timing properties that other animals do, but with some quantitative differences.

Scalar expectancy theory and peak-interval timing in humans.

There is epidemiologic and imaging evidence for the presence of cognitive reserve, but the neurophysiologic substrate of CR has not been established. In order to test the hypothesis that CR is related to aspects of neural processing, we used fMRI to image 19 healthy young adults while they performed a nonverbal recognition test. There were two task conditions. A low demand condition required encoding and recognition of single items and a titrated demand condition required the subject to encode and then recognize a larger list of items, with the study list size for each subject adjusted prior to scanning such that recognition accuracy was 75%. We hypothesized that individual differences in cognitive reserve are related to changes in neural activity as subjects moved from the low to the titrated demand task. To test this, we examined the correlation between subjects' fMRI activation and NART scores. This analysis was implemented voxel-wise in a whole brain fMRI dataset. During both the study and test phases of the recognition memory task we noted areas where, across subjects, there were significant positive and negative correlations between change in activation from low to titrated demand and the NART score. These correlations support our hypothesis that neural processing differs across individuals as a function of CR. This differential processing may help explain individual differences in capacity, and may underlie reserve against age-related or other pathologic changes.

/pdf/exploring-the-neural-basis-of-cognitive-reserve-79ha567xvg.pdf

Exploring the neural basis of cognitive reserve.

https://academiccommons.columbia.edu/doi/10.7916/D8N88P74/download

Age-related changes in brain activation during a delayed item recognition task.

https://academiccommons.columbia.edu/doi/10.7916/D8BV8V21/download

Brian C. Rakitin

Papers

Coupled Temporal Memories in Parkinson's Disease: A Dopamine-Related Dysfunction

Scalar expectancy theory and peak-interval timing in humans.

Exploring the neural basis of cognitive reserve.

Age-related changes in brain activation during a delayed item recognition task.

An event-related fMRI study of the neurobehavioral impact of sleep deprivation on performance of a delayed-match-to-sample task.