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.

Technological advances in rapid data acquisition have transformed medical biology into a data mining field, where new data sets are routinely dissected and analyzed by statistical models of ever-increasing complexity. Many hypotheses can be generated and tested within a single large data set, and even small effects can be statistically discriminated from a sea of noise. On the other hand, the development of therapeutic interventions moves at a much slower pace. They are determined from carefully randomized and well-controlled experiments with explicitly stated outcomes as the principal mechanism by which a single hypothesis is tested. In this paradigm, only a small fraction of interventions can be tested, and an even smaller fraction are ultimately deemed therapeutically successful. In this Review, we propose strategies to leverage large-cohort data to inform the selection of targets and the design of randomized trials of novel therapeutics. Ultimately, the incorporation of big data and experimental medicine approaches should aim to reduce the failure rate of clinical trials as well as expedite and lower the cost of drug development.

/pdf/the-promise-and-reality-of-therapeutic-discovery-from-large-3n1n6ei7or.pdf

The promise and reality of therapeutic discovery from large cohorts.

Lipids serve as metabolic substrates, structural components of cellular membranes, and signaling molecules. The steroidogenic machinery is compartmentalized at the organ, cellular, and subcellular level. Steroidogenic cells do not store premanufactured steroid hormones, and the rate-limiting step in the production of steroid hormones is the movement of substrate cholesterol to the inner mitochondrial membrane, where the first committed step in steroidogenesis takes place, which is the cholesterol side-chain cleavage reaction in which cholesterol is converted into pregnenolone. Several families of enzymes are involved in the synthesis of steroid hormones, the most important being the cytochrome P450 family and the hydroxysteroid dehydrogenases and reductases. In addition to steroid secreting glands, bioactive steroids are produced in small quantities in many cell types. Eicosanoids are derived enzymatically from 20-carbon polyunsaturated fatty acids (e.g., arachidonic acid). They are produced by almost all cells in response to hormonal stimulation or trauma, acting as paracrine or autocrine modulators. Specificity of eicosanoid action is afforded by selective expression of biosynthetic enzymes and their receptors. Eicosanoids include products of the cyclooxygenase (COX), lipoxygenase (LOX), and P450 enzyme acting on arachidonic acid and other polyunsaturated fatty acids. Prostanoids are formed by the COX enzymes. They are essential for ovulation and have been implicated in the processes of implantation, embryogenesis, and parturition.

Garret A. FitzGerald

Papers

The promise and reality of therapeutic discovery from large cohorts.

Steroid Hormones and Other Lipid Molecules Involved in Human Reproduction

A new synthetic approach for 4(S)-hydroxycyclopent-2-enone: a precursor to prostanoid synthesis

Analysis of isoprostanes

Chapter 4 – biochemical and functional effects of dietary substrate modification in man1