Cyclic AMP stimulates platelet-derived growth factor B chain mRNA expression in murine macrophage cell lines

Prostaglandin E2 plays a role in cytokine production presumably by altering intracellular levels of cAMP. In this paper, we report on the differential expression of cytokine genes in murine macrophages in response to stimulation with activators of cAMP. Macrophages were cultured with or without cAMP activators in the presence or absence of LPS. Prior to treatment, macrophages do not express interleukin-1β, but do express low levels of tumour necrosis factor α and platelet-derived growth factor B chain mRNAs. After culture with cAMP-inducers, including PGE2, dibutyryl cAMP and forskolin, PDGF B chain mRNA is induced. Forskolin, for example, induced expression PDGF B chain mRNA to a level ranging from 25% to 200% of the level induced by LPS in 6 h. In contrast, cAMP-inducers enhance the expression of IL-1β and TNF-α mRNAs, but only in the presence of LPS. The combination of forskolin and LPS does not appear to act synergistically on PDGF B chain mRNA levels, suggesting that LPS-stimulated effects are not mediated through a cAMP-dependent pathway. Furthermore, macrophages differentially express cytokine genes in response to treatment with inducers of intracellular cAMP

Heparan sulphate inhibition of cell proliferation induced by TGFβ and PDGF

The effect of glycosaminoglycans (GAGs) on the proliferation of smooth muscle cells (SMC) and fibroblasts was assessed by culturing cells with or without GAGs. Porcine heparan sulphate (HS) inhibited proliferation in a dose dependent manner. At 167 μg/ml of HS this reached 88% and 72% inhibition of SMC and fibroblast growth, respectively. Pig and beef mucosal heparins also blocked proliferation, but to a lesser extent. In contrast, beef lung heparin, chondroitin sulphate, and dermatan sulphate failed to block growth factor induced proliferation. Continuous presence of HS was not required, suggesting that the inhibitory effects resulted from a direct effect on the cell rather than an interaction of the GAG with growth factors. The mechanism by which GAGs inhibit proliferation will be addressed in future studies

Winners and losers as mangrove, coral and seagrass ecosystems respond to sea-level rise in Solomon Islands

A 2007 earthquake in the western Solomon Islands resulted in a localised subsidence event in which sea level (relative to the previous coastal settings) rose approximately 30-70 cm, providing insight into impacts of future rapid changes to sea level on coastal ecosystems. Here, we show that increasing sea level by 30-70 cm can have contrasting impacts on mangrove, seagrass and coral reef ecosystems. Coral reef habitats were the clear winners with a steady lateral growth from 2006-2014, yielding a 157% increase in areal coverage over seven years. Mangrove ecosystems, on the other hand, suffered the largest impact through a rapid dieback of 35% (130 ha) of mangrove forest in the study area after subsidence. These forests, however, had partially recovered seven years after the earthquake albeit with a different community structure. The shallow seagrass ecosystems demonstrated the most dynamic response to relative shifts in sea level with both losses and gains in areal extent at small scales of 10-100 m. The results of this study emphasize the importance of considering the impacts of sea-level rise within a complex landscape in which winners and losers may vary over time and space

Adipose Inflammation and Macrophage Infiltration After Binge Ethanol and Burn Injury

Ethanol exposure prior to traumatic injury, such as a burn, elevates systemic and local inflammatory responses and increases morbidity and mortality. Adipose is a large tissue mass that is often inflamed during obesity or other stresses which disturbs metabolic homeostasis. To date, there has been little investigation into the inflammatory response of adipose tissue after combined ethanol exposure and burn injury

Motivational Interviewing as an intervention to increase adolescent self-efficacy and promote weight loss: Methodology and design

<p>Abstract</p> <p>Background</p> <p>Childhood obesity is associated with serious physiological and psychological consequences including type 2 diabetes, higher rates of depression and low self-esteem. With the population of overweight and obese youth increasing, appropriate interventions are needed that speak to the issue of readiness to change and motivation to maintain adherence to healthy behavior changes. Motivational Interviewing (MI) is a method of therapy found to resolve ambivalence, enhance intrinsic motivation and promote confidence in a person's ability to make behavior changes. While MI has shown promise in the adult obesity literature as effecting positive lifestyle change, little is known about the effectiveness of MI with overweight and obese youth. This study aims to: 1) demonstrate that MI is an effective intervention for increasing a person's self-efficacy; 2) demonstrate that exposure to MI will facilitate healthy behavior changes; 3) explore psychological changes related to participation in MI and 4) compare physiological and anthropometric outcomes before and after intervention.</p> <p>Methods/Design</p> <p>The current investigation is a prospective study conducted with ongoing participants who regularly attend an outpatient pediatric care center for weight-loss. Overweight youth (BMI > 85^th%ile) between the ages of 10 and 18 who meet eligibility criteria will be recruited. Participants will be randomly assigned to a control group (social skills training) or a treatment group (MI). Participants will meet with the therapist for approximately 30 minutes prior to seeing the dietician, over the course of 6 months. Participants will also undergo a full day assessment at the beginning and end of psychology intervention to evaluate body fat, and metabolic risk (screening for diabetes, high cholesterol, high blood pressure and fitness level). The paper and pencil portions of the assessments as well as the clinical testing will occur at baseline and at the conclusion of the intervention (6 months) with a repeat assessment 6 months following the completion of the intervention.</p> <p>Discussion</p> <p>Results from this study are expected to enhance our understanding of the efficacy of MI with children and adolescents who are overweight or obese.</p> <p>Trial registration</p> <p>Current Controlled Trials #<a href="http://www.clinicaltrials.gov/ct2/show/NCT00326404">NCT00326404</a>.</p

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes