Increased Cardiac Myocyte PDE5 Levels in Human and Murine Pressure Overload Hypertrophy Contribute to Adverse LV Remodeling

Background

The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC).

Methodology/Principal Findings

In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dt_max and dP/dt_min with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro.

Conclusions/Significance

Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target.     

Impact of land‐use change to Jatropha bioenergy plantations on biomass and soil carbon stocks: a field study in Mali

Small‐scale Jatropha cultivation and biodiesel production have the potential of contributing to local development, energy security, and greenhouse gas (GHG) mitigation. In recent years however, the GHG mitigation potential of biofuel crops is heavily disputed due to the occurrence of a carbon debt, caused by CO₂ emissions from biomass and soil after land‐use change (LUC). Most published carbon footprint studies of Jatropha report modeled results based on a very limited database. In particular, little empirical data exist on the effects of Jatropha on biomass and soil C stocks. In this study, we used field data to quantify these C pools in three land uses in Mali, that is, Jatropha plantations, annual cropland, and fallow land, to estimate both the Jatropha C debt and its C sequestration potential. Four‐year‐old Jatropha plantations hold on average 2.3 Mg C ha^?1 in their above‐ and belowground woody biomass, which is considerably lower compared to results from other regions. This can be explained by the adverse growing conditions and poor local management. No significant soil organic carbon (SOC) sequestration could be demonstrated after 4 years of cultivation. While the conversion of cropland to Jatropha does not entail significant C losses, the replacement of fallow land results in an average C debt of 34.7 Mg C ha^?1, mainly caused by biomass removal (73%). Retaining native savannah woodland trees on the field during LUC and improved crop management focusing on SOC conservation can play an important role in reducing Jatropha's C debt. Although planting Jatropha on degraded, carbon‐poor cropland results in a limited C debt, the low biomass production, and seed yield attained on these lands reduce Jatropha's potential to sequester C and replace fossil fuels. Therefore, future research should mainly focus on increasing Jatropha's crop productivity in these degraded lands.     

Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients

Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.     

Surviving in Changing Seascapes: Sediment Dynamics as Bottleneck for Long-Term Seagrass Presence

Changes in the seascape often result in altered hydrodynamics that lead to coinciding changes in sediment dynamics. Little is known on how altered sediment dynamics affect long-term seagrass persistence. We studied the thresholds of sediment dynamics in relation to seagrass presence by comparing sediment characteristics and seagrass presence data of seven separate seagrass meadows. All meadows had a long-term (>20 years) presence. Within these meadows, we distinguish so-called “hotspots” (areas within a meadow where seagrass was found during all mapping campaigns) and “coldspots” (with infrequent seagrass presence). We monitored static sediment characteristics (median grain size, bulk density, silt content) and sediment dynamics (that is, bed level change and maximum sediment disturbance depth), bioturbation (that is, lugworm densities and induced fecal pit and mound relief), and seagrass cover. We statistically analyzed which sediment characteristic best explains seagrass cover. Densely vegetated hotspots were shown to have lower sediment dynamics than sparsely vegetated hotspots and coldspots, whereas static sediment characteristics were similar (grain size, bulk density). The vegetation cover was either low (2–15%) or high (>30%) and sediment dynamics showed a threshold for vegetation cover. From this correlative finding, we postulate a self-sustaining feedback of relatively dense seagrass via sediment stabilization and accordingly a runaway feedback once the seagrass cover becomes too sparse. The sensitivity for sediment dynamics shown in our study implies that future existence of seagrass meadows may be at risk as ongoing climate change might directly (increased environmental extremes) or indirectly (changing seascapes) negatively affect seagrass beds.     

Does plant size affect growth responses to water availability at glacial,modern and future CO<Subscript>2</Subscript> concentrations?

Plant responses to carbon (C) and water availability are strongly connected. Thus, we can learn much about the responses of modern plants to rising atmospheric carbon dioxide (CO₂) by studying their performance under a range of carbon and water availabilities, including very low CO₂ as in past glacial periods. We hypothesized that, especially in shallow soils, the positive effects of high CO₂ and the negative effects of low CO₂ on growth response to drought are moderated by plant size-driven feedbacks through transpiration and soil water depletion. We grew two temperate annual C₃ species, Avena sativa and Chenopodium album, in glacial (180 ppm), modern (400 ppm) and future (700 ppm) CO₂ levels and five soil water regimes in climate chambers. In both species, low CO₂ resulted in a much lower relative growth rate, biomass and total leaf area than at ambient CO₂ with higher water availability, but this difference disappeared steadily towards severe drought conditions. Elevated CO₂ increased relative growth rate, plant biomass and total leaf area of both species slightly compared with ambient CO₂. These results were especially pronounced under drought. Our results support the hypothesis that, in annuals, plant size modulates the negative drought effect at low CO₂. However, plant size-mediated effects of high CO₂ on growth response to drought were inconclusive. Further experiments should reveal the interactive effects of CO₂ and water regimes in environments closer to a field setting, both in shallow and in deep soils with unconstrained rooting, as well as in mixed communities.     

TLR- and NOD2-dependent regulation of human phagocyte-specific chitotriosidase

Human chitotriosidase is specifically expressed by phagocytes, has anti-fungal activity towards chitin-containing fungi in vitro and in vivo, and is part of innate immunity. We studied the effect of toll-like receptor (TLR)- and nucleotide-binding oligomerization domain (NOD)-2 triggering on chitotriosidase expression and release by phagocytes. We find that TLR, but not NOD2 activation, regulates chitotriosidase release by neutrophils. Furthermore, both TLR and NOD2 activation resulted in diminished induction by monocytes. Lastly, NOD2 activation, but not TLR stimulation, induces chitinase expression in macrophages. We conclude that phagocyte-specific regulation is important for efficient eradication of chitin-containing pathogens.