Differential Rates of Glycation Following Exposure to Unique Monosaccharides.

A complication of reducing sugars is that they can undergo Maillard chemical reactions, forming advanced glycation end-products (AGEs) that can induce oxidative stress and inflammation via engagements with the main receptor for AGEs (RAGE) in various tissues. Certain sugars, such as glucose and fructose, are well known to cause AGE formation. Recently, allulose has emerged as a rare natural sugar that is an epimer of fructose and which is of low caloric content that is minimally metabolized, leading to it being introduced as a low-calorie sugar alternative. However, the relative ability of allulose to generate AGEs compared to glucose and fructose is not known. Here we assess the accumulation of AGEs in cell-free, in vitro, and in vivo conditions in response to allulose and compare it to glycation mediated by glucose or fructose. AGEs were quantified in cell-free samples, cell culture media and lysates, and rat serum with glycation-specific ELISAs. In cell-free conditions, we observed concentration and time-dependent increases in AGEs when bovine serum albumin (BSA) was incubated with glucose or fructose and significantly less glycation when incubated with allulose. AGEs were significantly elevated when pulmonary alveolar type II-like cells were co-incubated with glucose or fructose; however, significantly less AGEs were detected when cells were exposed to allulose. AGE quantification in serum obtained from rats fed a high-fat, low-carb (HFLC) Western diet for 2 weeks revealed significantly less glycation in animals co-administered allulose compared to those exposed to stevia. These results suggest allulose is associated with less AGE formation compared to fructose or glucose, and support its safety as a low-calorie sugar alternative.

Different Lengths of Gestational Exposure to Secondhand Smoke or e-Cigarette Vapor Induce the Development of Placental Disease Symptoms.

Exposure to cigarette smoke is known to induce disease during pregnancy. Recent evidence showed that exposure to secondhand smoke (SHS) negatively impacts fetal and placental weights, leading to the development of intrauterine growth restriction (IUGR). Electronic cigarettes (eCigs) represent a phenomenon that has recently emerged, and their use is also steadily rising. Even so, the effects of SHS or eCigs during gestation remain limited. In the present study, we wanted to characterize the effects of SHS or eCig exposure at two different important gestational points during mouse pregnancy. C57/Bl6 mice were exposed to SHS or eCigs via a nose-only delivery system for 4 days (from 14.5 to 17.5 gestational days (dGA) or for 6 days (from 12.5 dGA to 17.5 dGA)). At the time of necropsy (18.5 dGA), placental and fetal weights were recorded, maternal blood pressure was determined, and a dipstick test to measure proteinuria was performed. Placental tissues were collected, and inflammatory molecules in the placenta were identified. Treatment with SHS showed the following: (1) a significant decrease in placental and fetal weights following four days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. Treatment with eCigs showed the following: (1) a significant decrease in placental weight and fetal weight following four or six days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. We also observed different inflammatory markers associated with the development of IUGR or PE. We conclude that the detrimental effects of SHS or eCig treatment coincide with the length of maternal exposure. These results could be beneficial in understanding the long-term effects of SHS or eCig exposure in the development of placental diseases.

Inflammatory Cytokine Elaboration Following Secondhand Smoke (SHS) Exposure Is Mediated in Part by RAGE Signaling.

The receptor for advanced glycation end products (RAGE) is a key contributor to immune and inflammatory responses in myriad diseases. RAGE is a transmembrane pattern recognition receptor with a special interest in pulmonary anomalies due to its naturally abundant pulmonary expression. Our previous studies demonstrated an inflammatory role for RAGE following acute 30-day exposure to secondhand smoke (SHS), wherein immune cell diapedesis and cytokine/chemokine secretion were accentuated in part via RAGE signaling. However, the chronic inflammatory mechanisms associated with RAGE have yet to be fully elucidated. In this study, we address the impact of long-term SHS exposure on RAGE signaling. RAGE knockout (RKO) and wild-type (WT) mice were exposed to SHS using a nose-only delivery system (Scireq Scientific, Montreal, Canada) for six months. SHS-exposed animals were compared to mice exposed to room air (RA) only. Immunoblotting was used to assess the phospho-AKT and phospho-ERK activation data, and colorimetric high-throughput assays were used to measure NF-kB. Ras activation was measured via ELISAs. Bronchoalveolar lavage fluid (BALF) cellularity was quantified, and a mouse cytokine antibody array was used to screen the secreted cytokines. The phospho-AKT level was decreased, while those of phospho-ERK, NF-kB, and Ras were elevated in both groups of SHS-exposed mice, with the RKO + SHS-exposed mice demonstrating significantly decreased levels of each intermediate compared to those of the WT + SHS-exposed mice. The BALF contained increased levels of diverse pro-inflammatory cytokines in the SHS-exposed WT mice, and diminished secretion was detected in the SHS-exposed RKO mice. These results validate the role for RAGE in the mediation of chronic pulmonary inflammatory responses and suggest ERK signaling as a likely pathway that perpetuates RAGE-dependent inflammation. Additional characterization of RAGE-mediated pulmonary responses to prolonged exposure will provide a valuable insight into the cellular mechanisms of lung diseases such as chronic obstructive pulmonary disease.

Decreased Expression of Pulmonary Homeobox NKX2.1 and Surfactant Protein C in Developing Lungs That Over-Express Receptors for Advanced Glycation End-Products (RAGE).

Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors of the immunoglobin superfamily prominently expressed by lung epithelium. Previous experiments demonstrated that over-expression of RAGE by murine alveolar epithelium throughout embryonic development causes neonatal lethality coincident with significant lung hypoplasia. In the current study, we evaluated the expression of NKX2.1 (also referred to as TTF-1), a homeodomain-containing transcription factor critical for branching morphogenesis, in mice that differentially expressed RAGE. We also contextualized NKX2.1 expression with the abundance of FoxA2, a winged double helix DNA binding protein that influences respiratory epithelial cell differentiation and surfactant protein expression. Conditional RAGE over-expression was induced in mouse lung throughout gestation (embryonic day E0-18.5), as well as during the critical saccular period of development (E15.5-18.5), and analyses were conducted at E18.5. Histology revealed markedly less lung parenchyma beginning in the canalicular stage of lung development and continuing throughout the saccular period. We discovered consistently decreased expression of both NKX2.1 and FoxA2 in lungs from transgenic (TG) mice compared to littermate controls. We also observed diminished surfactant protein C in TG mice, suggesting possible hindered differentiation and/or proliferation of alveolar epithelial cells under the genetic control of these two critical transcription factors. These results demonstrate that RAGE must be specifically regulated during lung formation. Perturbation of epithelial cell differentiation culminating in respiratory distress and perinatal lethality may coincide with elevated RAGE expression in the lung parenchyma.

Altered Epigenetic Profiles in the Placenta of Preeclamptic and Intrauterine Growth Restriction Patients.

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are placental pathologies known to complicate pregnancy and cause neonatal disorders. To date, there is a limited number of studies on the genetic similarity of these conditions. DNA methylation is a heritable epigenetic process that can regulate placental development. Our objective was to identify methylation patterns in placental DNA from normal, PE and IUGR-affected pregnancies. DNA was extracted, and bisulfite was converted, prior to being hybridized for the methylation array. Methylation data were SWAN normalized and differently methylated regions were identified using applications within the USEQ program. UCSC's Genome browser and Stanford's GREAT analysis were used to identify gene promoters. The commonality among affected genes was confirmed by Western blot. We observed nine significantly hypomethylated regions, two being significantly hypomethylated for both PE and IGUR. Western blot confirmed differential protein expression of commonly regulated genes. We conclude that despite the uniqueness of methylation profiles for PE and IUGR, the similarity of some methylation alterations in pathologies could explain the clinical similarities observed with these obstetric complications. These results also provide insight into the genetic similarity between PE and IUGR and suggest possible gene candidates plausibly involved in the onset of both conditions.

Lung Inflammation Is Associated with Preeclampsia Development in the Rat.

Preeclampsia (PE) is an obstetric complication associated with significant health implications for the fetus and mother. Studies have shown a correlation between lung disease development and PE. Gas6 protein is expressed in the lung and placenta, and binds to the AXL Tyrosine kinase receptor. Recently, our laboratory utilized Gas6 to induce preeclamptic-like conditions in rats. Our objective was to determine the role of Gas6/AXL signaling in the maternal lung during PE development. Briefly, pregnant rats were divided into control, Gas6, or Gas6 + R428 (an AXL inhibitor). Immunofluorescence was performed to determine AXL expression. Bronchoalveolar lavage fluid (BALF) was procured for the assessment of inflammatory cell secretion. Western blot was performed to detect signaling molecules and ELISA determined inflammatory cytokines. We observed increased proteinuria and increased blood pressure in Gas6-treated animals. AXL was increased in the lungs of the treated animals and BALF fluid revealed elevated total protein abundance in Gas6 animals. Extracellular-signal regulated kinase (ERK) and protein kinase B (AKT) signaling in the lung appeared to be mediated by Gas6 as well as the secretion of inflammatory cytokines. We conclude that Gas6 signaling is capable of inducing PE and that this is associated with increased lung inflammation.

Integrated assessment of the food-water-land-ecosystems nexus in Europe: Implications for sustainability.

Climate and socio-economic change impacts are likely to cross traditional sectoral and regional boundaries with cascading indirect, and potentially far-reaching, repercussions. This is particularly important for the food-water-land-ecosystems (FWLE) nexus, which is fundamental for the achievement of at least six of the seventeen Sustainable Development Goals (SDGs). A holistic understanding of the FWLE nexus interactions and how and to what extent various exogenous drivers of change affect them is therefore central to cross-sectoral adaptation planning. Here, we present such an integrated assessment for Europe applying a regional Integrated Assessment Platform (IAP). The study explores a wide range of future climate and socio-economic scenarios using more than 900 model simulations. The results show that food production is likely to be the main driver of Europe's future landscape change dynamics (with or without climate change). Agriculture and land use allocation is often driven by complex cross-sectoral interactions with cascading effects on other sectors such as forestry, biodiversity, and water under the various scenarios. The modelling also highlighted that while sustaining current levels of food production at the European level could be achievable under most climate and socio-economic scenarios, there are significant regional differences with winners and losers. The analysis raises the question of whether current production and consumption policies are sustainable in the long-term. Such systematic integrated model-based analysis plays a crucial role in informing development of cross-sectoral policies that maximise synergies and minimise trade-offs across nexus sectors, regions, and scenarios. This is essential to achieve the SDGs.

Agricultural livelihoods in coastal Bangladesh under climate and environmental change--a model framework.

Coastal Bangladesh experiences significant poverty and hazards today and is highly vulnerable to climate and environmental change over the coming decades. Coastal stakeholders are demanding information to assist in the decision making processes, including simulation models to explore how different interventions, under different plausible future socio-economic and environmental scenarios, could alleviate environmental risks and promote development. Many existing simulation models neglect the complex interdependencies between the socio-economic and environmental system of coastal Bangladesh. Here an integrated approach has been proposed to develop a simulation model to support agriculture and poverty-based analysis and decision-making in coastal Bangladesh. In particular, we show how a simulation model of farmer's livelihoods at the household level can be achieved. An extended version of the FAO's CROPWAT agriculture model has been integrated with a downscaled regional demography model to simulate net agriculture profit. This is used together with a household income-expenses balance and a loans logical tree to simulate the evolution of food security indicators and poverty levels. Modelling identifies salinity and temperature stress as limiting factors to crop productivity and fertilisation due to atmospheric carbon dioxide concentrations as a reinforcing factor. The crop simulation results compare well with expected outcomes but also reveal some unexpected behaviours. For example, under current model assumptions, temperature is more important than salinity for crop production. The agriculture-based livelihood and poverty simulations highlight the critical significance of debt through informal and formal loans set at such levels as to persistently undermine the well-being of agriculture-dependent households. Simulations also indicate that progressive approaches to agriculture (i.e. diversification) might not provide the clear economic benefit from the perspective of pricing due to greater susceptibility to climate vagaries. The livelihood and poverty results highlight the importance of the holistic consideration of the human-nature system and the careful selection of poverty indicators. Although the simulation model at this stage contains the minimum elements required to simulate the complexity of farmer livelihood interactions in coastal Bangladesh, the crop and socio-economic findings compare well with expected behaviours. The presented integrated model is the first step to develop a holistic, transferable analytic method and tool for coastal Bangladesh.

Simulating yield response of rice to salinity stress with the AquaCrop model.

The FAO AquaCrop model has been widely applied throughout the world to simulate crop responses to deficit water applications. However, its application to saline conditions is not yet reported, though saline soils are common in coastal areas. In this study, we parameterized and tested AquaCrop to simulate rice yield under different salinity regimes. The data and information required in the model were collected through a field experiment at the Bangladesh Agricultural Research Institute, Gazipur. The experiment was conducted with the BRRI Dhan28, a popular boro rice variety in Bangladesh, with five levels of saline water irrigation, three replicates for each level. In addition, field monitoring was carried out at Satkhira in the southwest coastal region of Bangladesh to collect data and information based on farmers' practices and to further validate the model. The results indicated that the AquaCrop model with most of its default parameters could replicate the variation of rice yield with the variation of salinity reasonably well. The root mean square error and mean absolute error of the model yield were only 0.12 t per ha and 0.03 t per ha, respectively. The crop response versus soil salinity stress curve was found to be convex in shape with a lower threshold of 2 dS m(-1), an upper threshold of 10 dS m(-1) and a shape factor of 2.4. As the crop production system in the coastal belt of Bangladesh has become vulnerable to climate induced sea-level rise and the consequent increase in water and soil salinity, the AquaCrop would be a useful tool in assessing the potential impact of these future changes as well as other climatic parameters on rice yield in the coastal region.

Myoblasts from intrauterine growth-restricted sheep fetuses exhibit intrinsic deficiencies in proliferation that contribute to smaller semitendinosus myofibres.

Intrauterine growth restriction (IUGR) reduces skeletal muscle mass in fetuses and offspring. Our objective was to determine whether myoblast dysfunction due to intrinsic cellular deficiencies or serum factors reduces myofibre hypertrophy in IUGR fetal sheep. At 134 days, IUGR fetuses weighed 67% less (P < 0.05) than controls and had smaller (P < 0.05) carcasses and semitendinosus myofibre areas. IUGR semitendinosus muscles had similar percentages of pax7-positive nuclei and pax7 mRNA but lower (P < 0.05) percentages of myogenin-positive nuclei (7 ± 2% and 13 ± 2%), less myoD and myogenin mRNA, and fewer (P < 0.05) proliferating myoblasts (PNCA-positive-pax7-positive) than controls (44 ± 2% vs. 52 ± 1%). Primary myoblasts were isolated from hindlimb muscles, and after 3 days in growth media (20% fetal bovine serum, FBS), myoblasts from IUGR fetuses had 34% fewer (P < 0.05) myoD-positive cells than controls and replicated 20% less (P < 0.05) during a 2 h BrdU pulse. IUGR myoblasts also replicated less (P < 0.05) than controls during a BrdU pulse after 3 days in media containing 10% control or IUGR fetal sheep serum (FSS). Both myoblast types replicated less (P < 0.05) with IUGR FSS-supplemented media compared to control FSS-supplemented media. In differentiation-promoting media (2% FBS), IUGR and control myoblasts had similar percentages of myogenin-positive nuclei after 5 days and formed similar-sized myotubes after 7 days. We conclude that intrinsic cellular deficiencies in IUGR myoblasts and factors in IUGR serum diminish myoblast proliferation and myofibre size in IUGR fetuses, but intrinsic myoblast deficiencies do not affect differentiation. Furthermore, the persistent reduction in IUGR myoblast replication shows adaptive deficiencies that explain poor muscle growth in IUGR newborn offspring.

Algal wastewater treatment systems for seasonal climates: application of a simple modelling approach to generate local and regional design guidelines.

Algal waste stabilisation ponds (WSP) provide a means of treating wastewater, and also a potential source of water for re-use in irrigation, aquaculture or algal biomass cultivation. The quantities of treated water available and the periods in which it is suitable for use or discharge are closely linked to climatic factors. This paper describes the application, at a continent-wide scale, of a modelling approach based on the use of readily available climate datasets to provide WSP design and performance guidelines linked to geographical location. Output is presented in regionally-based contour maps covering a wide area of Russia and central Asia and indicating pond area, earliest discharge date, discharge duration, wastewater inflow:outflow ratio and salinity under user-specified conditions. The results confirm that broad-brush discharge guidelines of the type commonly used in North America can safely be applied; but suggest that a more detailed approach is worthwhile to optimise operating regimes for local conditions. The use of long-series climate data can also permit tailoring of designs to specific sites. The work considers a simple 2-pond system, but other configurations and operating regimes should be investigated, especially for the wide range of locations across the world that are intermediate between the 'one short discharge per year' mode and year-round steady-state operation.