e activity transforming growth SB-705498 factor beta receptor activity two-component sensor activity Cellular component clathrin adaptor complex axon part tight junction lamellipodium CUL4 RING ubiquitin ligase complex actin filament Axin-APC-beta-catenin-GSK3B complex Schmidt-Lanterman incisure AP-type membrane coat adaptor complex endomembrane system Choriodecidual Infection Induces Fetal Lung Injury Functional Analysis of a Network Diseases and Disorders Inflammatory response Connective tissue disorders Inflammatory disease Skeletal and muscular disorders Immunological disease Number of Molecules 169 144 203 144 169Molecular and Cellular Functions Cellular movement Cell-to-cell signaling and interaction Antigen presentation Cellular growth and proliferation Cell death 137 138 88 187 127 Physiological Systems Immune cell trafficking Hematological system development Tissue development Tissue morphology Organismal survival 126 168 142 84 51 Canonical Pathway Analysis Top Canonical Pathways Antigen presentation pathway Dendritic cell maturation TREM1 signaling Allograft rejection signaling Communication between innate and adaptive immune cells Ratio Transcription Factor Analysis Top Transcription Factors NF-kB STAT3 STAT1 CEBPA SPI1 Predicted Activation State Activated Activated Activated Activated Activated p-value of overlap 4.80610229 1.13610222 2.70610220 4.31610219 9.71610217 The Functional Analysis of a Network identified biological functions and/or diseases that 10336422 were most significant to the molecules in the network using a right-tailed Fisher’s exact test. Canonical Pathway Analysis identified pathways from the IPA library 19470764 that were most significant to the data set. Significance of the association was measured in two ways: as the ratio of the number of molecules from the focus gene set that map to the pathway to the total number of molecules that map to the canonical pathway and using Fisher’s exact test. Transcription factor analysis is based on prior knowledge of expected effects between transcription factors and their target genes stored in the IPA library. The overlap p-value measures whether there is a statistically significant overlap between the dataset genes and the genes regulated by a transcription factor using Fisher’s Exact 
Test. doi:10.1371/journal.pone.0046863.t005 arteries demonstrated by medial smooth muscle hypertrophy and increased adventitial fibrosis.. The strength of our study lies in the similarities in lung development and immune function between the nonhuman primate and human neonate. Pulmonary morphologic and immune features in our model also emulate that in humans, but differ from many other species. Both humans and nonhuman primates lack pulmonary intravascular macrophages present in the lungs of many species which tend to concentrate toxins and bacteria in the lungs. In contrast, humans and nonhuman primates localize bacteria and toxins in the liver and spleen, which makes their lungs less susceptible to injury than other species. There are also many similarities to human pregnancy including a singleton fetus with a long gestational period, hemomonochorial placentation, and sensitivity to pathogens. Maternal-fetal inflammatory responses induced by infection and parturition also emulate that in humans, but differ significantly in other animal models. Many mammalian models in which lung development has been studied are also in the alveolar stage of lung development, which is more advanced at the time of a preterm
