Structured Abstract Objective Lipid phosphate phosphatase 3 (LPP3), encoded by the PPAP2B gene, is an integral membrane enzyme that dephosphorylates, and thereby terminates, the G-protein-coupled receptor-mediated signaling actions of lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). LPP3 is essential for normal vascular development in mice, and a common PPAP2B polymorphism is associated with increased risk of coronary artery disease in humans. Herein, we investigate the function of endothelial LPP3 to understand its role in development and human disease. Approach and results We developed mouse models with selective LPP3 deficiency in endothelial and hematopoietic cells. Tyrosine kinase Tek (Tie2) promoter-mediated inactivation of Ppap2b resulted in embryonic lethality due to vascular defects. LPP3 deficiency in adult mice, achieved using a tamoxifen-inducible Cre transgene under the control of the Tie2 promoter, enhanced local and systemic inflammatory responses. Endothelial, but not hematopoietic, cell LPP3-deficiency led to significant increases in vascular permeability at baseline, and enhanced sensitivity to inflammation-induced vascular leak. Endothelial barrier function was restored by pharmacological or genetic inhibition of either LPA production by the circulating lysophospholipase D autotaxin or of G-protein-coupled receptor-dependent LPA signaling. Conclusions Our results identify a role for the autotaxin/LPA-signaling nexus as a mediator of endothelial permeability in inflammation and demonstrate that LPP3 limits these effects. These findings have implications for therapeutic targets to maintain vascular barrier function in inflammatory states.

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Bovine brucellosis, caused by Brucella abortus, is a serious zoonotic disease manifested by reproductive disorders resulting in huge economic losses to dairy farmers. A random survey was conducted to study the epidemiology of brucellosis in Punjab (India) using sampling software Survey Toolbox. Two-stage sampling procedure was adopted; in the first step, villages were selected randomly from sampling frame of all the villages of Punjab followed by selection of owners, and animals in individual farms were identified using random sampling. In all, 32 villages were selected and then 345 animals (approximately 5%) were sampled from these villages. The milk samples collected were screened for brucella antibodies employing ELISA test. The overall apparent prevalence of brucellosis was found to be 18.26% (true prevalence -17.68%). The prevalence in the central zone of the state was significantly higher, viz. 23.2% (chi square = 11.34, p < 0.01) compared to 14.2% in the sub-mountainous zone and 5.8% in the arid irrigated zone. The disease prevalence was found to be non-significantly higher (chi square 1.029, p = 0.310) in cattle (20.67%) compared to buffaloes (16.41%) and increased with age (chi square = 8.572, p < 0.05) in both species. There was significant association between disease and abortion (chi square = 22.322, p < 0.01) and maximum abortion cases due to brucellosis were found in > 6 month of gestation (95.7%). The disease was significantly associated with the retention of placenta (chi square = 8.477, p < 0.01), however there was no significant relationship of the disease with repeat breeding (chi square = 0.044, p = 0.834). The results of the study suggested that the accurate epidemiological scenario of the disease may be obtained by employing multistage sampling procedures using milk-based ELISA.