Anthrax toxin, which is released from the Gram-positive bacterium Bacillus anthracis, is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA binds a receptor on the surface of the target cell and further assembles into a homo-heptameric pore through which EF and LF translocate into the cytosol. Two distinct cellular receptors for anthrax toxin, TEM8/ANTXR1 and CMG2/ANTXR2, have been identified, and it is known that their extracellular domains bind PA with low and high affinities, respectively. Here, we report the crystal structure of the TEM8 extracellular vWA domain at 1.7 Å resolution. The overall structure has a typical integrin fold and is similar to that of the previously published CMG2 structure. In addition, using structure-based mutagenesis, we demonstrate that the putative interface region of TEM8 with PA (consisting of residues 56, 57, and 154–160) is responsible for the PA-binding affinity differences between the two receptors. In particular, Leu56 was shown to be a key factor for the lower affinity of TEM8 towards PA compared with CMG2. Because of its high affinity for PA and low expression in normal tissues, an isolated extracellular vWA domain of the L56A TEM8 variant may serve as a potent antitoxin and a potential therapeutic treatment for anthrax infection. Moreover, as TEM8 is often over-expressed in tumor cells, our TEM8 crystal structure may provide new insights into how to design PA mutants that preferentially target tumor cells.

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The relationship between asthma and temperature changes remains controversial. The aim of this study was to investigate the association between temperature changes and the risk of asthma. A total of 26 studies (combined total number of subjects N > 26 million), covering 13 countries and Costa Rica, were identified by using a series of keywords in different combinations and searching the papers in PubMed, EMBSEA, Web of Science, MEDLINE, AIM, LILACS, and WPRIM before February 2016. Most of the papers were published in English. Random-effects meta-analyses were performed to evaluate the effect of temperature drop on risk of asthma. Several secondary analyses were also calculated based on stratification for different age, season, latitude, and region on risk of asthma. The odds ratio (OR) estimate between temperature drop and asthma was 1.05 (95% CI 1.02, 1.08) in the meta-analysis. For children, the overall OR was 1.09 (95% CI 1.03, 1.15). Dose-effect analyses showed stronger associations in asthma risk for each 1°1 °C decrement in short-term temperature (OR 1.055, 95% CI 1.00, 1.11). Further stratifications showed that winter (OR 1.03, 95% CI 1.01, 105) and low latitude (OR 1.72, 95% CI 1.23, 2.41) have a statistically significant association with the increased risk of asthma. Exposure of people to short-term temperature drop (per 1 °C decrement) was significantly associated with the risk of lower respiratory tract infections (LRTI) with asthma (OR 1.02, 95% CI 1.00, 1.04). Results suggest an adverse effect of temperature drop on asthma risk, especially in children and low-latitude areas. It may be opportune to consider the preventive actions against temperature drop, including simple face masks, to decrease the risk of asthma.