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

https://www.healio.com/psychiatry/journals/psycann/1976-12-6-12/{806b8887-c02e-40c8-a228-57f1cdb2bdba}/the-stress-of-life.pdf

The stress of life

/pdf/multiple-factor-analysis-1xkff91jny.pdf

Multiple factor analysis.

The neuroscience of exercise is a growing research area that is dedicated to furthering our understanding of the effects that exercise has on mental health and athletic performance. The present study examined three specific topics: (1) the relationship between exercise and mental disorders (e.g. major depressive disorder, dementia and Parkinson's disease), (2) the effects of exercise on the mood and mental health of athletes, and (3) the possible neurobiological mechanisms that mediate the effects of exercise. Positive responses to regular physical exercise, such as enhanced functional capacity, increased autonomy and improved self-esteem, are frequently described in the recent literature, and these responses are all good reasons for recommending regular exercise. In addition, physical exercise may improve both mood and adherence to an exercise program in healthy individuals and might modulate both the performance and mental health of athletes. Exercise is associated with the increased synthesis and release of both neurotransmitters and neurotrophic factors, and these increases may be associated with neurogenesis, angiogenesis and neuroplasticity. This review is a call-to-action that urges researchers to consider the importance of understanding the neuroscience of physical exercise and its contributions to sports science.

/pdf/neuroscience-of-exercise-from-neurobiology-mechanisms-to-5es39jvoj8.pdf

Neuroscience of Exercise: From Neurobiology Mechanisms to Mental Health

In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies--treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism--are needed to reverse or improve HAND-related neurological dysfunction.

HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

Ovarian hormone elevations are associated with enhanced learning/memory. During behavioral estrus or pregnancy, progestins, such as progesterone (P(4)) and its metabolite 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), are elevated due, in part, to corpora luteal and placental secretion. During 'pseudopregnancy', the induction of corpora luteal functioning results in a hormonal milieu analogous to pregnancy, which ceases after about 12 days, due to the lack of placental formation. Multiparity is also associated with enhanced learning/memory, perhaps due to prior steroid exposure during pregnancy. Given evidence that progestins and/or parity may influence cognition, we investigated how natural alterations in the progestin milieu influence cognitive performance. In Experiment 1, virgin rats (nulliparous) or rats with two prior pregnancies (multiparous) were assessed on the object placement and recognition tasks, when in high-estrogen/P(4) (behavioral estrus) or low-estrogen/P(4) (diestrus) phases of the estrous cycle. In Experiment 2, primiparous or multiparous rats were tested in the object placement and recognition tasks when not pregnant, pseudopregnant, or pregnant (between gestational days (GDs) 6 and 12). In Experiment 3, pregnant primiparous or multiparous rats were assessed daily in the object placement or recognition tasks. Females in natural states associated with higher endogenous progestins (behavioral estrus, pregnancy, multiparity) outperformed rats in low progestin states (diestrus, non-pregnancy, nulliparity) on the object placement and recognition tasks. In earlier pregnancy, multiparous, compared with primiparous, rats had a lower corticosterone, but higher estrogen levels, concomitant with better object placement performance. From GD 13 until post partum, primiparous rats had higher 3 alpha,5 alpha-THP levels and improved object placement performance compared with multiparous rats.

/pdf/estrous-cycle-pregnancy-and-parity-enhance-performance-of-31ez7maiva.pdf

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks.

Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance.

https://www.gaming.ny.gov/gaming/20140409forum/Wulfert%20(SUNY-Albany)/Supplemental%20Material/Paris%20et%20al,%20Sex%20differences%20in%20salivary%20cortisol%20in%20response%20to%20acute%20stressors,%20Hormonal%20Behavior%2057(1)%2035-45%20(2010).pdf

Sex differences in salivary cortisol in response to acute stressors among healthy participants, in recreational or pathological gamblers, and in those with posttraumatic stress disorder.

Gambling Pathology is Associated with Dampened Cortisol Response Among Men and Women

Rationale
Human immunodeficiency virus (HIV) infection is associated with substantial increases in generalized anxiety. The HIV regulatory protein, transactivator of transcription (Tat), has been implicated in the neuropathogenesis related to HIV-1 infection. However, direct examination of the effect of Tat on behavioral measures of anxiety has not been demonstrated.

/pdf/anxiety-like-behavior-of-mice-produced-by-conditional-5ddoh363t0.pdf

Jason J. Paris

Papers

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks.

Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance.

Sex differences in salivary cortisol in response to acute stressors among healthy participants, in recreational or pathological gamblers, and in those with posttraumatic stress disorder.

Gambling Pathology is Associated with Dampened Cortisol Response Among Men and Women

Anxiety-like behavior of mice produced by conditional central expression of the HIV-1 regulatory protein, Tat