Summary To directly test the contribution of Scgb1a1+ Clara cells to postnatal growth, homeostasis and repair of lung epithelium, we generated a Scgb1a1-CreERTM “knock-in” mouse line for lineage tracing these cells. Under all conditions tested the majority of Clara cells in the bronchioles both self-renew and generate ciliated cells. In the trachea, Clara cells give rise to ciliated cells but do not self-renew extensively. Nevertheless, they can contribute to tracheal repair. In the postnatal mouse lung it has been proposed that bronchioalveolar stem cells (BASCs) which co-express Scgb1a1 (Secretoglobin1a1) and SftpC (Surfactant Protein C), contribute descendants to both bronchioles and alveoli. The putative BASCs were lineage labeled in our studies. However, we find no evidence for the function of a special BASC population during postnatal growth, adult homeostasis or repair. Rather, our results support a model in which the trachea, bronchioles and alveoli are maintained by distinct populations of epithelial progenitor cells.

Oral Conditions and Pregnancy (OCAP) is a 5-year prospective study of pregnant women designed to determine whether maternal periodontal disease contributes to the risk for prematurity and growth restriction in the presence of traditional obstetric risk factors. Full-mouth periodontal examinations were conducted at enrollment (prior to 26 weeks gestational age) and again within 48 hours postpartum to assess changes in periodontal status during pregnancy. Maternal periodontal disease status at antepartum, using a 3-level disease classification (health, mild, moderate-severe) as well as incident periodontal disease progression during pregnancy were used as measures of exposures for examining associations with the pregnancy outcomes of preterm birth by gestational age (GA) and birth weight (BW) adjusting for race, age, food stamp eligibility, marital status, previous preterm births, first birth, chorioamnionitis, bacterial vaginosis, and smoking. Interim data from the first 814 deliveries demonstrate that maternal periodontal disease at antepartum and incidence/progression of periodontal disease are significantly associated with a higher prevalence rate of preterm births, BW < 2,500 g, and smaller birth weight for gestational age. For example, among periodontally healthy mothers the unadjusted prevalence of births of GA < 28 weeks was 1.1%. This was higher among mothers with mild periodontal disease (3.5%) and highest among mothers with moderate-severe periodontal disease (11.1%). The adjusted prevalence rates among GA outcomes were significantly different for mothers with mild periodontal disease (n = 566) and moderate-severe disease (n = 45) by pair-wise comparisons to the periodontally healthy reference group (n = 201) at P = 0.017 and P < 0.0001, respectively. A similar pattern was seen for increased prevalence of low birth weight deliveries among mothers with antepartum periodontal disease. For example, there were no births of BW < 1000 g among periodontally healthy mothers, but the adjusted rate was 6.1% and 11.4% for mild and moderate-severe periodontal disease (P = 0.0006 and P < 0.0001), respectively. Periodontal disease incidence/progression during pregnancy was associated with significantly smaller births for gestational age adjusting for race, parity, and baby gender. In summary, the present study, although preliminary in nature, provides evidence that maternal periodontal disease and incident progression are significant contributors to obstetric risk for preterm delivery, low birth weight and low weight for gestational age. These studies underscore the need for further consideration of periodontal disease as a potentially new and modifiable risk for preterm birth and growth restriction.

ABSTRACT:Reactive oxygen species (ROS) serve as cell signaling molecules for normal biologic processes. However, the generation of ROS can also provoke damage to multiple cellular organelles and processes, which can ultimately disrupt normal physiology. An imbalance between the production of ROS and the antioxidant defenses that protect cells has been implicated in the pathogenesis of a variety of diseases, such as cancer, asthma, pulmonary hypertension, and retinopathy. The nature of the injury will ultimately depend on specific molecular interactions, cellular locations, and timing of the insult. This review will outline the origins of endogenous and exogenously generated ROS. The molecular, cellular, pathologic, and physiologic targets will then be discussed with a particular emphasis on aspects relevant to child development. Finally, antioxidant defenses that scavenge ROS and mitigate associated toxicities will be presented, with a discussion of potential therapeutic approaches for the prevention and/or treatment of human diseases using enzymatic and nonenzymatic antioxidants. . This review will focus on-1) origins of ROS: environment, cells, and cellular components; 2) molecular targets: classic and novel macromolecular targets and associated toxicity in infants and children; 3) antioxidant defenses: developmental regulation and vulnerabilities; and 4) antioxidant therapies: enzymatic and nonenzymatic approaches. Origins of ROSOxygen has a unique molecular structure and is abundant within cells. It readily accepts free electrons generated by normal oxidative metabolism within the cell, producing ROS, such as O 2 ·Ϫ and hydroxyl radical (HO · ), as well as the oxidant H 2 O 2 . Processes causing uncoupling of electron transport can enhance the production of ROS, with mitochondria being a major source (4). However, other cellular components, such as endoplasmic reticulum-bound enzymes, cytoplasmic enzyme systems, and the surface of the plasma membrane, also contribute (5,6). Activity of multiple enzyme systems, such as the cytochrome P 450 monoxygenase system, xanthine oxidoreductase, nitric oxide synthases, and several others involved in the inflammatory process (cyclooxygenase and lipoxygenase), can also increase the generation of ROS.

Accumulating evidence suggests that outdoor air pollution may have a significant impact on central nervous system (CNS) health and disease. To address this issue, the National Institute of Environmental Health Sciences/National Institute of Health convened a panel of research scientists that was assigned the task of identifying research gaps and priority goals essential for advancing this growing field and addressing an emerging human health concern. Here, we review recent findings that have established the effects of inhaled air pollutants in the brain, explore the potential mechanisms driving these phenomena, and discuss the recommended research priorities/approaches that were identified by the panel.