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.

Urinary 8-EPI PGF2α: an index of oxidant stress in vivo*

Biosynthesis of P450 products of arachidonic acid in humans: increased formation in cardiovascular disease.

Aside from their established role in initiating the vascular occlusive events that culminate in myocardial infarction and stroke, platelets are increasingly appreciated for their relevance to inflammation and carcinogenesis An overview of randomized trials of antiplatelet drugs, mostly aspirin, indicates that they reduce the secondary incidence of important vascular events by ≈20%,1 and provocative albeit inconclusive evidence has emerged, suggestive of their value in cancer2 Most experience has been gathered with aspirin, which suppresses platelet cyclooxygenase-1–derived thromboxane (Tx)A2 formation and antagonists of the P2Y12 platelet adenosine diphosphate (ADP) receptor, such as ticlopidine, clopidogrel, and prasugrel3

Article, see p 595 

A problem with antiplatelet drugs, as with anticoagulant drugs (those targeting elements of the coagulation cascade which are favored for assembly on the membranes of activated platelets), is the segregation of clinical benefit from the risk of bleeding In the acute clinical setting, such as in patients with ST elevation and myocardial infarction (STEMI), prevention of thrombosis is paramount Here, potent inhibition of platelet function is the objective, such as can be attained with parenteral administration of inhibitors of the platelet integrin, αIIbβIII: bleeding is tolerated, especially if it occurs at a site where it can be controlled, such as at the point of catheter insertion4 However, during chronic drug administration, such as in the secondary prevention of MI, even nuisance bleeds, which in themselves are not life-threatening, drive down the degree of platelet inhibition that is practical, given their impact on patient compliance Drugs that block individual pathways of platelet activation rather than a final step, such as fibrinogen binding of αIIbβIII, have found favor in this setting However, even low dose aspirin roughly doubles the low incidence of serious gastrointestinal bleeds compared with placebo, and the …

Platelet microRNAs: Novy Mir* or mired in human complexity?

The imbalance between the roughly constant rate of new drug approvals and the exploding cost estimates of drug development—mostly the cost of failure—has raised concern about the declining productivity of the pharmaceutical industry. Efforts to address the situation have included an investment in human capital—particularly those individuals who can project science across the translational divide (bench to clinic)—and investment in infrastructure, as exemplified by Clinical and Translational Science Awards in the United States and Biomedical Research Centers in the United Kingdom, and an increase in partnerships between academia and industry ( 1 ). However, radical reform of the iron rules of intellectual property (IP) worldwide will be necessary if we are to harvest and integrate the efforts of scientists and clinicians scattered across companies, universities, and countries, best qualified to generate new therapies.

http://science.sciencemag.org/content/sci/338/6106/483.full.pdf

Can Intellectual Property Save Drug Development

In this Editorial, co-Chief Scientific Advisors of Science Translational Medicine, Elazer Edelman and Garret FitzGerald, discuss challenges and opportunities for the next decade of translational research.

https://stm.sciencemag.org/content/scitransmed/11/489/eaax4327.full.pdf

Garret A. FitzGerald

Papers

Urinary 8-EPI PGF2α: an index of oxidant stress in vivo*

Biosynthesis of P450 products of arachidonic acid in humans: increased formation in cardiovascular disease.

Platelet microRNAs: Novy Mir* or mired in human complexity?

Can Intellectual Property Save Drug Development

A decade of Science Translational Medicine