Project description:When compressed by the shrinking alveolar surface area during exhalation, films of pulmonary surfactant in situ reduce surface tension to levels at which surfactant monolayers collapse from the surface in vitro. Vesicles of pulmonary surfactant added below these monolayers slow collapse. X-ray scattering here determined the structural changes induced by the added vesicles. Grazing incidence X-ray diffraction on monolayers of extracted calf surfactant detected an ordered phase. Mixtures of dipalmitoyl phosphatidylcholine and cholesterol, but not the phospholipid alone, mimic that structure. At concentrations that stabilize the monolayers, vesicles in the subphase had no effect on the unit cell, and X-ray reflection showed that the film remained monomolecular. The added vesicles, however, produced a concentration-dependent increase in the diffracted intensity. These results suggest that the enhanced resistance to collapse results from enlargement by the additional material of the ordered phase.
Project description:The amount of pulmonary surfactant within type II cells and in the alveolar space, referred to as surfactant pool sizes, are tightly regulated. The molecular pathways that sense and regulate surfactant pool size within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. Our data show that mice with a germline mutation in the orphan G-protein-coupled receptor, GPR116, have a 30-fold accumulation of surfactant phospholipids that causes respiratory distress in adult animals. This phenotype is associated with increased surfactant secretion and induction of the purinergic receptor P2RY2 in young animals, and lipid-laden macrophages and alveolar destruction in older animals. We further demonstrate that GPR116 mRNA expression is developmentally regulated in the murine lung with peak expression at birth when surfactant pool sizes are maximal. Within the lung, GPR116 protein expression is restricted to the apical plasma membrane of alveolar type I and type II epithelial cells. To better understand the roles and molecular mechanisms by which Gpr116 influences gene expression in lung, the effect of cell-selective deletion of Gpr116 (Gpr116D/D) on genome-wide mRNA expression profiles was determined in murine type II alveolar epithelial cells. Differentially expressed genes were identified from Affymetrix Murine GeneChips analysis and subjected to gene ontology classification promoter analysis, pathway mapping and literature mining.
Project description:The amount of pulmonary surfactant within type II cells and in the alveolar space, referred to as surfactant pool sizes, are tightly regulated. The molecular pathways that sense and regulate surfactant pool size within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. Our data show that mice with a germline mutation in the orphan G-protein-coupled receptor, GPR116, have a 30-fold accumulation of surfactant phospholipids that causes respiratory distress in adult animals. This phenotype is associated with increased surfactant secretion and induction of the purinergic receptor P2RY2 in young animals, and lipid-laden macrophages and alveolar destruction in older animals. We further demonstrate that GPR116 mRNA expression is developmentally regulated in the murine lung with peak expression at birth when surfactant pool sizes are maximal. Within the lung, GPR116 protein expression is restricted to the apical plasma membrane of alveolar type I and type II epithelial cells.
Project description:Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after birth. Mutations in genes regulating surfactant homeostasis have been associated with severe lung disease in neonates and older infants. Biophysical and transgenic mouse models have provided insight into the mechanisms underlying surfactant protein and alveolar homeostasis. These studies have provided the framework for understanding the structure and function of pulmonary surfactant, which has informed understanding of the pathogenesis of diverse pulmonary disorders previously considered idiopathic. This review considers the pulmonary surfactant system and the genetic causes of acute and chronic lung disease caused by disruption of alveolar homeostasis.
Project description:1. Pulmonary surfactant was isolated from rats that had been exposed to chrysotile asbestos dust for from 3 days to 15 weeks. 2. Asbestos-treated rats showed a progressive increase in amounts of surfactant. After 15 weeks, treated animals contained 4 times as much as non-treated. 3. No significant change was seen in the total protein or total fatty acid composition of surfactant with exposure. 4. The increase in surfactant phosphatidylcholine normally seen on maturation of rat lung was accelerated by exposure of animals to asbestos. 5. An increase in the activity of phosphorylcholine glyceride transferase in lung homogenates and free cell populations was found. 6. Lysosomal phospholipase A was relatively unaffected by dust exposure. 7. It is suggested that the increase in surfactant amounts could be due to an increase in its synthesis without a corresponding alteration in its degradation.
Project description:Cannibalism in insects plays an important role in ecological relationships. Nonetheless, it has not been studied as extensively as in other arthropods groups (e.g., Arachnida). From a theoretical point of view, cannibalism has an impact on the development of more realistic stage-structure mathematical models. Additionally, it has a practical application for biological pest control, both in mass-rearing and out in the field through inoculative releases. In this paper, the cannibalistic behavior of two species of predatory bugs was studied under laboratory conditions-one of them a generalist predator (strictly carnivorous), Nabis pseudoferus, and the other a true omnivore (zoophytophagous), Nesidiocoris tenuis-and compared with the intraguild predation (IGP) behavior. The results showed that cannibalism in N. pseudoferus was prevalent in all the developmental stages studied, whereas in N. tenuis, cannibalism was rarely observed, and it was restricted mainly to the first three nymphal stages. Cannibalism and intraguild predation had no linear relationship with the different cannibal-prey size ratios, as evaluated by the mortality rates and survival times, although there were variations in cannibalism between stages, especially for N. pseudoferus. The mathematical model's implications are presented and discussed.
Project description:BackgroundThe EAT-Lancet Commission drew on all available nutritional and environmental evidence to construct the first global benchmark diet capable of sustaining health and protecting the planet, but it did not assess dietary affordability. We used food price and household income data to estimate affordability of EAT-Lancet benchmark diets, as a first step to guiding interventions to improve diets around the world.MethodsWe obtained retail prices from 2011 for 744 foods in 159 countries, collected under the International Comparison Program. We used these data to identify the most affordable foods to meet EAT-Lancet targets. We compared total diet cost per day to each country's mean per capita household income, calculated the proportion of people for whom the most affordable EAT-Lancet diet exceeds total income, and also measured affordability relative to a least-cost diet that meets essential nutrient requirements.FindingsThe most affordable EAT-Lancet diets cost a global median of US$2·84 per day (IQR 2·41-3·16) in 2011, of which the largest share was the cost of fruits and vegetables (31·2%), followed by legumes and nuts (18·7%), meat, eggs, and fish (15·2%), and dairy (13·2%). This diet costs a small fraction of average incomes in high-income countries but is not affordable for the world's poor. We estimated that the cost of an EAT-Lancet diet exceeded household per capita income for at least 1·58 billion people. The EAT-Lancet diet is also more expensive than the minimum cost of nutrient adequacy, on average, by a mean factor of 1·60 (IQR 1·41-1·78).InterpretationCurrent diets differ greatly from EAT-Lancet targets. Improving diets is affordable in many countries but for many people would require some combination of higher income, nutritional assistance, and lower prices. Data and analysis for the cost of healthier foods are needed to inform both local interventions and systemic changes.FundingBill & Melinda Gates Foundation.
Project description:This work explores the potential for strategizing pulmonary surfactant (PS) for drug delivery over the respiratory air-liquid interface: the interfacial delivery. The efficacy of PS- and interface-assisted drug vehiculization was determined both in vitro and in vivo using a native purified porcine PS combined with the hydrophobic anti-inflammatory drug Tacrolimus (TAC), a calcineurin inhibitor. In vitro assays were conducted in a novel double surface balance setup designed to emulate compression-expansion dynamics applied to interfacially connected drug donor and recipient compartments. In this setup, PS transported TAC efficiently over air-liquid interfaces, with compression/expansion breathing-like dynamics enhancing rapid interface-assisted diffusion and drug release. The efficacy of PS-assisted TAC vehiculization was also evaluated in vivo in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). In anesthetized mice, TAC combined with PS was intra-nasally (i.n) instilled prior administering i.n. LPS. PS/TAC pre-treatment caused greater TAC internalization into a higher number of lung cells obtained from bronchoalveolar lavages (BAL) than TAC pre-treatment alone. Additionally, the PS/TAC combination but not TAC or PS alone attenuated the LPS-induced pro-inflammatory effects reducing cells and proteins in BAL fluid. These findings indicated that PS-mediated increase in TAC uptake blunted the pro-injurious effects of LPS, suggesting a synergistic anti-inflammatory effect of PS/drug formulations. These in vitro and in vivo results establish the potential utility of PS to open novel effective delivery strategies for inhaled drugs.
Project description:Monomolecular films at an air/water interface coexist at the equilibrium spreading tension (?(e)) with the bulk phase from which they form. For individual phospholipids, ?(e) is single-valued, and separates conditions at which hydrated vesicles adsorb from tensions at which overcompressed monolayers collapse. With pulmonary surfactant, isotherms show that monolayers compressed on the surface of bubbles coexist with the three-dimensional collapsed phase over a range of surface tensions. ?(e) therefore represents a range rather than a single value of surface tension. Between the upper and lower ends of this range, rates of collapse for spread and adsorbed films decrease substantially. Changes during adsorption across this narrow region of coexistence between the two- and three-dimensional structures at least partially explain how alveolar films of pulmonary surfactant become resistant to collapse.
Project description:Plant-based diets have been linked to both health benefits and a lower climate impact. However, plant-based diets may represent both healthy and unhealthy dietary practices. The present study aimed to develop a nationally adapted healthy plant-based diet based on the global EAT-Lancet reference diet. Development took place in a series of steps. First, the original EAT-Lancet reference diet was evaluated based on food availability, i.e., using Danish food data (Model 1). Then, the model was further modified to reflect national food based dietary guidelines (FBDG) and characteristics of current consumption pattern, e.g., by including processed food, discretionary foods and beverages in the diet (Model 2). The contents of macronutrients, vitamins and minerals, except for vitamin D and iodine, were found to be sufficient for Model 2, according to the recommended nutrient density to be used for planning diets for groups of individuals aged 6-65 years. In addition, the study gave an insight into the nutrients and foods to be aware of in planning a predominantly plant-based diet, thereby providing directions for future revisions of sustainable FBDGs. These include a stronger emphasis on the intake of legumes, nuts and seeds, fruit and vegetables including dark green vegetables, whole-grain products and vegetable oils as well as lowering meat intake.