Neutrophils have recently been shown to release DNA-based extracellular traps that contribute to microbicidal killing and have also been implicated in autoimmunity. The role of neutrophil extracellular trap (NET) formation in the host response to nonbacterial pathogens has received much less attention. Here, we show that the protozoan pathogen Toxoplasma gondii elicits the production of NETs from human and mouse neutrophils. Tachyzoites of each of the three major parasite strain types were efficiently entrapped within NETs, resulting in decreased parasite viability. We also show that Toxoplasma activates a MEKextracellular signal-regulated kinase (ERK) pathway in neutrophils and that the inhibition of this pathway leads to decreased NET formation. To determine if Toxoplasma induced NET formation in vivo, we employed a mouse intranasal infection model. We found that the administration of tachyzoites by this route induced a rapid tissue recruitment of neutrophils with evidence of extracellular DNA release. Taken together, these data indicate a role for NETs in the host innate response to protozoan infection. We propose that NET formation limits infection by direct microbicidal effects on Toxoplasma as well as by interfering with the ability of the parasite to invade target host cells.

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Changes of Land Use and Land Cover (LULC) affect atmospheric, climatic, and biological spheres of the earth. Accurate LULC map offers detail information for resources management and intergovernmental cooperation to debate global warming and biodiversity reduction. This paper examined effects of pansharpening and atmospheric correction on LULC classification. Object-Based Support Vector Machine (OB-SVM) and Pixel-Based Maximum LikelihoodClassifier (PB-MLC) were applied for LULC classification. Results showed that atmospheric correction is not necessary for LULC classification if it is conducted in the original multispectral image. Nevertheless, pansharpening plays much more important roles on the classification accuracy than the atmospheric correction. It can help to increase classification accuracy by 12% on average compared to the ones without pansharpening. PB-MLC and OB-SVM achieved similar classification rate. This study indicated that the LULC classification accuracy using PB-MLC and OB-SVM is 82% and 89% respectively. A combination of atmospheric correction, pansharpening, and OB-SVM could offer promising LULC maps from WorldView-2 multispectral and panchromatic images.

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Mycobacterium tuberculosis (Mtb) DprE1, an essential isomerase for the biosynthesis of the mycobacterial cell wall, is a validated target for tuberculosis (TB) drug development. Here we report the X‐ray crystal structures of DprE1 and the DprE1 resistant mutant (Y314C) in complexes with TCA1 derivatives to elucidate the molecular basis of their inhibitory activities and an unconventional resistance mechanism, which enabled us to optimize the potency of the analogs. The selected lead compound showed excellent in vitro and in vivo activities, and low risk of toxicity profile except for the inhibition of CYP2C9. A crystal structure of CYP2C9 in complex with a TCA1 analog revealed the similar interaction patterns to the DprE1–TCA1 complex. Guided by the structures, an optimized molecule was generated with differential inhibitory activities against DprE1 and CYP2C9, which provides insights for development of a clinical candidate to treat TB.

The effects of felbamate on the pharmacokinetics of a low-dose combination oral contraceptive containing 30 micrograms ethinyl estradiol and 75 micrograms gestodene were assessed in a randomized, double-blind, placebo-controlled parallel-group study in healthy premenopausal female volunteers established in a regimen of oral contraceptive use. They received either placebo or 2400 mg/day felbamate from midcycle (day 15) to midcycle (day 14) of two consecutive oral contraceptive cycles (months 1 and 2). Pharmacokinetic assessments of ethinyl estradiol and gestodene were performed on day 14 of both cycles. To determine whether ovulation occurred, plasma progesterone and urinary luteinizing hormone levels were measured, and diaries recording vaginal bleeding were kept. Felbamate treatment resulted in a significant 42% decrease in gestodene area under the plasma concentration-time curve (0 to 24 hours) (p = 0.018) compared with baseline, whereas a minor but not clinically relevant effect was observed on the pharmacokinetic parameters of ethinyl estradiol. There were no changes in the pharmacokinetics of ethinyl estradiol or gestodene after placebo treatment. No volunteer showed hormonal evidence of ovulation; however, one volunteer reported the onset of intermenstrual bleeding during felbamate treatment. Because of the effect of felbamate on the pharmacokinetics of gestodene and the report of intermenstrual bleeding, it is possible that the contraceptive efficacy of low-dose combination oral contraceptives may be adversely affected during felbamate treatment.