There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

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.

J. Appl. Cryst.の発刊に際して

Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors. Traditional inflammation and pain relief drugs target both cyclooxygenase 1 and 2 (COX-1 and COX-2), causing severe side effects. Here, the authors use in situ click chemistry to develop COX-2 specific inhibitors with high in vivo anti-inflammatory activity.

/pdf/in-situ-click-chemistry-generation-of-cyclooxygenase-2-zyy8rhnlnx.pdf

In situ click chemistry generation of cyclooxygenase-2 inhibitors

https://journals.iucr.org/m/issues/2021/02/00/me6114/me6114.pdf

Structure and mechanism of copper–carbonic anhydrase II: a nitrite reductase. Corrigendum

Carbonic anhydrases (CAs) have been linked to tumor progression, particularly membrane-bound CA isoform IX (CA IX). The role of CA IX in the context of breast cancer is to regulate the pH of the tumor microenvironment. In contrast to CA IX, expression of CA XII, specifically in breast cancer, is associated with better outcome despite performing the same catalytic function. In this study, we have structurally modeled the orientation of bound ureido-substituted benzene sulfonamides (USBs) within the active site of CA XII, in comparison to CA IX and cytosolic off-target CA II, to understand isoform specific inhibition. This has identified specific residues within the CA active site, which differ between isoforms that are important for inhibitor binding and isoform specificity. The ability of these sulfonamides to block CA IX activity in breast cancer cells is less effective than their ability to block activity of the recombinant protein (by one to two orders of magnitude depending on the inhibitor). The same is true for CA XII activity but now they are two to three orders of magnitude less effective. Thus, there is significantly greater specificity for CA IX activity over CA XII. While the inhibitors block cell growth, without inducing cell death, this again occurs at two orders of magnitude above the Ki values for inhibition of CA IX and CA XII activity in their respective cell types. Surprisingly, the USBs inhibited cell growth even in cells where CA IX and CA XII expression was ablated. Despite the potential for these sulfonamides as chemotherapeutic agents, these data suggest that we reconsider the role of CA activity on growth potentiation.

/pdf/selective-inhibition-of-ca-ix-over-ca-xii-using-benzene-1uyyomif6o.pdf

Selective inhibition of CA IX over CA XII using benzene sulfonamides in breast cancer cells: Disconnect between CA activity and growth inhibition

Clinical vignette The patient is a 75-year-old female with a 40-pack-year smoking history. Low dose lung screening computed tomography (CT) scan found a 1-cm left upper lobe (LUL) mass. The patient denies any hemoptysis, weight loss, bone pain or neuro status changes. Her pulmonary function tests are not normal. Her pulmonary function tests demonstrated that the forced expiratory volume (FEV1) was 58% of predicted FEV1 and 80% of predicted diffusion lung capacity (DLCO). A lingular sparing LUL apical trisegmentectomy was thus planned.

/pdf/minimally-invasive-vats-left-upper-lobe-apical-1raaaxw9ed.pdf

Minimally invasive VATS left upper lobe apical trisegmentectomy.

Author(s): Drouin, Lauren M; Lins, Bridget; Janssen, Mandy; Bennett, Antonette; Chipman, Paul R; McKenna, Robert; Chen, Weijun; Muzyczka, Nicholas; Cardone, Giovanni; Baker, Timothy S; Agbandje-McKenna, Mavis

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/47EB51B6D5CECA75A85491CF487EC6D8/S1431927616006516a.pdf/div-class-title-structural-rearrangements-in-r432a-variant-of-aav2-affect-genome-packaging-div.pdf

Structural Rearrangements in R432A Variant of AAV2 Affect Genome Packaging

SUMMARY Anatomic lung resection remains the gold standard in the treatment of lung cancer. The traditional approach has been an open thoracotomy with anatomic lobectomy. The approach to the operation has continued to evolve, transitioning from large thoracotomy incisions to smaller muscle sparing incisions to video-assisted thoracic surgery. This article reviews the studies and evidence in support of the potential benefits afforded by the video-assisted thoracic surgery approach in the treatment of lung cancer.

Robert McKenna

Papers

Structure and mechanism of copper–carbonic anhydrase II: a nitrite reductase. Corrigendum

Selective inhibition of CA IX over CA XII using benzene sulfonamides in breast cancer cells: Disconnect between CA activity and growth inhibition

Minimally invasive VATS left upper lobe apical trisegmentectomy.

Structural Rearrangements in R432A Variant of AAV2 Affect Genome Packaging

Benefits of video-assisted thoracoscopic surgery in the treatment of non-small-cell lung cancer