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

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

/pdf/free-radicals-in-the-physiological-control-of-cell-function-g3w3iyr0ph.pdf

Free Radicals in the Physiological Control of Cell Function

The REDCap consortium: Building an international community of software platform partners.

Comprehensive Integration of Single-Cell Data.

Five healthy normotensive volunteers (mean ± SEM age 29.6 ± 4.6 years) were infused with l -noradrenaline for a 15 min period every 3 hours for 24 hours from 0900. The concentrations of l -noradrenaline used were 0.02. 0.03, 0.05 [μg·kg−1·min−1, preceded by a saline infusion, each step lasting 5 min. The lowest preinfusion blood pressures and heart rates were at 0300 and 0600, the range being 1.45 kPa (11.6 mmHg) systolic, 1.33 kPa (10.0 mmHg) diastolic pressure, and 12.2 beats·min−1, heart rate.

The slope of the log-dose response curve relating systolic pressure to infused noradrenaline was significantly reduced at 0300 compared with 0900 (P <0.05) and at 1200 compared with 1500 (P < 0.05). Baroreflex sensitivity as measured by the regression of mean RR interval on systolic pressure, was maximal at 1200 and 0300. The circadian variation to tilt was studied in the same subjects on a separate occasion. Mean tilted minus mean lying systolic pressure was least at 1200 and 0300. Supine plasma noradrenaline did not differ with clock time, but on tilt to 70° head up, plasma noradrenaline was significantly lower at 1200 and 0300 than at 0900 and 1500 respectively (P <0.05). The slope of RR interval on systolic pressure in response to tilt is significantly increased at 1200 and 0300 compared with 0900 and 2100 (P <0.05). These results suggest a decline in adrenergic vascular reactivity and an increase in the gain of the baroreflex at 1200 and 0300.

Circadian rhythm of baroreflex reactivity and adrenergic vascular response.

Influenza is a leading cause of respiratory mortality and morbidity. While inflammation is essential for fighting infection, a balance of anti-viral defense and host tolerance is necessary for recovery. Circadian rhythms have been shown to modulate inflammation. However, the importance of diurnal variability in the timing of influenza infection is not well understood. Here we demonstrate that endogenous rhythms affect survival in influenza infection. Circadian control of influenza infection is mediated by enhanced inflammation as proven by increased cellularity in bronchoalveolar lavage (BAL), pulmonary transcriptomic profile and histology and is not attributable to viral burden. Better survival is associated with a time dependent preponderance of NK and NKT cells and lower proportion of inflammatory monocytes in the lung. Further, using a series of genetic mouse mutants, we elucidate cellular mechanisms underlying circadian gating of influenza infection.

/pdf/circadian-control-of-lung-inflammation-in-influenza-4tk4nz9myi.pdf

Circadian control of lung inflammation in influenza infection.

Thromboxane synthesis and action within the kidney.

Rapid, Agonist-dependent Phosphorylation in Vivo of Human Thromboxane Receptor Isoforms MINIMAL INVOLVEMENT OF PROTEIN KINASE C

In COVID-19, complement activation may contribute to hemostatic activation leading to pathological features such as microvascular injury and coagulopathy.

/pdf/covid-19-microangiopathy-hemostatic-activation-and-21kbfla5ul.pdf

Garret A. FitzGerald

Papers

Circadian rhythm of baroreflex reactivity and adrenergic vascular response.

Circadian control of lung inflammation in influenza infection.

Thromboxane synthesis and action within the kidney.

Rapid, Agonist-dependent Phosphorylation in Vivo of Human Thromboxane Receptor Isoforms MINIMAL INVOLVEMENT OF PROTEIN KINASE C

COVID-19, microangiopathy, hemostatic activation, and complement.