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

This article concerns the nature of evoked brain responses and the principles underlying their generation. We start with the premise that the sensory brain has evolved to represent or infer the causes of changes in its sensory inputs. The problem of inference is well formulated in statistical terms. The statistical fundaments of inference may therefore afford important constraints on neuronal implementation. By formulating the original ideas of Helmholtz on perception, in terms of modern-day statistical theories, one arrives at a model of perceptual inference and learning that can explain a remarkable range of neurobiological facts. It turns out that the problems of inferring the causes of sensory input (perceptual inference) and learning the relationship between input and cause (perceptual learning) can be resolved using exactly the same principle. Specifically, both inference and learning rest on minimizing the brain’s free energy, as defined in statistical physics. Furthermore, inference and learning can proceed in a biologically plausible fashion. Cortical responses can be seen as the brain’s attempt to minimize the free energy induced by a stimulus and thereby encode the most likely cause of that stimulus. Similarly, learning emerges from changes in synaptic efficacy that minimize the free energy, averaged over all stimuli encountered. The underlying scheme rests on empirical Bayes and hierarchical models of how sensory input is caused. The use of hierarchical models enables the brain to construct prior expectations in a dynamic and context-sensitive fashion. This scheme provides a principled way to understand many aspects of cortical organization and responses. The aim of this article is to encompass many apparently unrelated anatomical, physiological and psychophysical attributes of the brain within a single theoretical perspective. In terms of cortical architectures, the theoretical treatment predicts that sensory cortex should be arranged hierarchically, that connections should be reciprocal and that forward and backward connections should show a functional asymmetry (forward connections are driving, whereas backward connections are both driving and modulatory). In terms of synaptic physiology, it predicts associative plasticity and, for dynamic models, spike-timing-dependent plasticity. In terms of electrophysiology, it accounts for classical and extra classical receptive field effects and long-latency or endogenous components of evoked cortical responses. It predicts the attenuation of responses encoding prediction error with perceptual learning and explains many phenomena such as repetition suppression, mismatch negativity (MMN) and the P300 in electroencephalography. In psychophysical terms, it accounts for the behavioural correlates of these physiological phenomena, for example, priming and global precedence. The final focus of this article is on perceptual learning as measured with the MMN and the implications for empirical studies of coupling among cortical areas using evoked sensory responses.

/pdf/a-theory-of-cortical-responses-2aiw9zqf1h.pdf

A theory of cortical responses

INTRODUCTION The issue of social rehabilitation and reintegration (hereafter social reintegration2) is mentioned under the third strategy target of the EU Action Plan 2000–2004. The third EU strategy target is to 'substantially increase the number of successfully treated addicts', and point 3.1.3.4 instructs that 'Member States [are] to ensure that adequate attention is paid to social and professional rehabilitation and reintegration of former addicts'. However, social reintegration is also linked to social exclusion, which is mentioned in chapter 2 of the EU Action Plan, where it is stated that 'the EMCDDA [is] to develop indicators on drug-related crime, the availability of illicit drugs (including at street level) and drug-related social exclusion'. For the EMCDDA, social reintegration comes under strategy target four – that is, as a response to social exclusion – however, target two is clearly also relevant. Social exclusion is often perceived as a cause of problem drug use, although many see it as a consequence of problem drug use. We will not elaborate on this further here, except to note that social exclusion and problem drug use are two phenomena that are very closely interlinked and that social reintegration is a possible response to both. The EMCDDA Programme 2, 'Analysis of responses', set out to identify how social reintegration is understood in each Member State and to map the availability of social reintegration facilities in Member States according to these national perceptions. It became evident at an early stage that this would be a complex task, involving extensive data collection, as national reports generally provided insufficient data on this specific subject. eight countries turned out to be difficult to map and so, in February 2002, the EMCDDA launched a call for tender for a project, 'Mapping social reintegration services in EU countries'. 3 The aim of this project was to describe the state of the art of social reintegration in the following eight countries: The research specifications, to investigate 'the state of the art of social reintegration', suggested that the following should be identified for each of the eight countries: 1 Other contributors will be mentioned in the respective chapters. 2 Our country studies so far have shown that the term 'rehabilitation' is used ambiguously across Europe – from low-threshold refuges, to normal treatment, to actual reintegration into society. For this reason, we shall use the term 'social reintegration' in this report, as this is used much more …

European Monitoring Centre for Drugs and Drug Addiction

The mismatch negativity (MMN) in basic research of central auditory processing: a review.

Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics. Language: en

Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.

Results: Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. Conclusions: The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDARrelated dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/481683/yoa9366b.pdf

Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers: Implications for Models of Cognitive Deficits in Schizophrenia

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

https://www.maps.org/images/pdf/1998_vollenweider_1.pdf

Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naïve Healthy Volunteers

https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(08)00154-5.pdf

Franz X. Vollenweider

Papers

Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.

Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers: Implications for Models of Cognitive Deficits in Schizophrenia

The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naïve Healthy Volunteers

Serotonin research: contributions to understanding psychoses.