Novel acylflavones from Sideritis syriaca ssp. syriaca

In the framework of the detailed phytochemical analysis of the aerial parts of Sideritis syriaca, two novel acylflavones were isolated together with three acetylated flavone glycosides and acylated flavone glycosides. The novel acylflavones were identified as isoscutellarein 7-trans-p-coumarate and apigenin 7-,4′-bis(trans-p-coumarate). Their structures were elucidated by means of UV, 1D and 2D NMR, LC–DAD–MS and confirmed by HR-MS spectroscopy.     

The Interplay between Aquaporin-1 and the Hypoxia-Inducible Factor 1α in a Lipopolysaccharide-Induced Lung Injury Model in Human Pulmonary Microvascular Endothelial Cells

Aquaporin-1 (AQP1), a water channel, and the hypoxia-inducible factor 1α (HIF1A) are implicated in acute lung injury responses, modulating among others pulmonary vascular leakage. We hypothesized that the AQP1 and HIF1A systems interact, affecting mRNA, protein levels and function of AQP1 in human pulmonary microvascular endothelial cells (HPMECs) exposed to lipopolysaccharide (LPS). Moreover, the role of AQP1 in apoptosis and wound healing progression was examined. Both AQP1 mRNA and protein expression levels were higher in HPMECs exposed to LPS compared to untreated HPMECs. However, in the LPS-exposed HIF1A-silenced cells, the mRNA and protein expression levels of AQP1 remained unaltered. In the permeability experiments, a statistically significant volume increase was observed at the 360 s time-point in the LPS-exposed HPMECs, while LPS-exposed HIF1A-silenced HPMECs did not exhibit cell swelling, implying a dysfunctional AQP1. AQP1 did not seem to affect cell apoptosis yet could interfere with endothelial migration and/or proliferation. Based on our results, it seems that HIF1A silencing negatively affects AQP1 mRNA and protein expression, as well as AQP1 function, in the setting of lung injury.     

Non-steady state modeling of extracellular polymeric substances,soluble microbial products,and active and inert biomass

We present a modeling approach that quantifies the unified theory presented in the companion paper. In this approach, we use mathematical modeling to quantify the relationships among three solid species--bacteria, extracellular polymeric substances (EPS), and inert residual biomass-two soluble microbial products (SMP), original substrate, and an electron acceptor. According to the model, donor electrons are used for the synthesis of biomass, EPS, and utilization-associated products. Residual inert biomass and biomass-associated products are produced from the decay of active biomass and the hydrolysis of EPS, respectively. The model includes mass balance equations that consistently describe the flow of electrons among the components. It is solved with a set of parameters appropriate to the experimental study of Hsieh et al. (Biotech. Bioeng. 44 (1994) 219). Model outputs capture all trends observed in steady-state CSTR experiments and transient batch experiments. This agreement supports that the unified theory correctly captures the interconnections among SMP, EPS, and active and inert biomass.     

Evaluating trends in biofilm density using the UMCCA model

We present a series of modeling cases that illustrate the trends described by the unique features of the unified multiple-component cellular automaton (UMCCA) model for a heterogeneous, two-dimensional biofilm. The outputs of the UMCCA model show five general trends. (1) The concentration profiles for the two soluble microbial products are opposite the profile for original substrate. (2) The top of the biofilm is dominated by active biomass and EPS, while the bottom is dominated by residual inert biomass. Within the top layers, active biomass has a much higher concentration than EPS. (3) The top of all biofilm is quite "fluffy," while the bottom is dense. (4) The peak of the composite density does not correspond to the peak of active biomass. (5) All biomass types show considerable local heterogeneity. The series of cases also indicate what conditions lead to particular characteristics observed in some biofilms. Biofilm clusters are promoted by substrate limitation, a high detachment rate, or strong consolidation. A high biofilm density is associated with an old biofilm, which is favored by a low substrate concentration, a high detachment rate, and strong consolidation. Old biofilms also can develop low-density pockets near the substratum, a possible cause of sloughing. Local heterogeneity is generally related to the same factors that cause a high density. We also solved the UMCCA model for conditions similar to the experiments of Bishop et al. (Water Sci. Technol. 31(1) (1995) 143), who measured the total biomass density in layers from the substratum. The model outputs captured all the major trends in the experimental data: the overall thickness and density of biofilms increase with time, and the total biomass density is 5-10 times greater near the substratum than near the top of the biofilm. Furthermore, the model indicates that the residual inert biomass becomes denser toward the substratum, a trend observed experimentally; the UMCCA model suggests that this trend is due to the combined effects of consolidation and inert biomass having a larger maximum density.     

A unified theory for extracellular polymeric substances,soluble microbial products,and active and inert biomass

We present a critical review of the relationships among three microbial products: extracellular polymeric substances (EPS), soluble microbial products (SMP), and inert biomass. Up to now, two different "schools" of researchers have treated these products separately. The "EPS school" has considered active biomass and EPS, while the "SMP school" has considered active biomass, SMP, and inert biomass. Here, we provide a critical review of each of the microbial products. Then, we develop a unified theory that couples them and reconciles apparent contradictions. In our unified theory, cells use electrons from the electron-donor substrate to build active biomass, and they also produce bound EPS and utilization-associated products (UAP) at the same time and in proportion to substrate utilization. Bound EPS are hydrolyzed to biomass-associated products (BAP), while active biomass undergoes endogenous decay to form residual dead cells. Finally, UAP and BAP, being biodegradable, are utilized by active biomass as recycled electron-donors substrates. Our unified theory shows that the apparently distinct products from the SMP and EPS schools overlap each other. Soluble EPS is actually SMP, or the sum of UAP and BAP. Furthermore, active biomass, as defined by the SMP school, includes bound EPS, while inert biomass includes bound EPS and the residual dead cells.     

Modeling the development of biofilm density including active bacteria, inert biomass, and extracellular polymeric substances

We present the unified multi-component cellular automaton (UMCCA) model, which predicts quantitatively the development of the biofilm's composite density for three biofilm components: active bacteria, inert or dead biomass, and extracellular polymeric substances. The model also describes the concentrations of three soluble organic components (soluble substrate and two types of soluble microbial products) and oxygen. The UMCCA model is a hybrid discrete-differential mathematical model and introduces the novel feature of biofilm consolidation. Our hypothesis is that the fluid over the biofilm creates pressures and vibrations that cause the biofilm to consolidate, or pack itself to a higher density over time. Each biofilm compartment in the model output consolidates to a different degree that depends on the age of its biomass. The UMCCA model also adds a cellular automaton algorithm that identifies the path of least resistance and directly moves excess biomass along that path, thereby ensuring that the excess biomass is distributed efficiently. A companion paper illustrates the trends that the UMCCA model is able to represent and shows a comparison with experimental results.     

Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus: An Update of Experimental and Clinical Evidence

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell types depending on receptor interactions and local stimuli. Beyond its extensively studied anti-tumor and immunomodulatory properties, a growing body of experimental and clinical evidence over the past two decades suggests a protective role of TRAIL in the development of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. This evidence can be briefly summarized by the following observations: (i) acceleration and exacerbation of T1DM and T2DM by TRAIL blockade or genetic deficiency in animal models, (ii) prevention and amelioration of T1DM and T2DM with recombinant TRAIL treatment or systemic TRAIL gene delivery in animal models, (iii) significantly reduced circulating soluble TRAIL levels in patients with T1DM and T2DM both at disease onset and in more advanced stages of diabetes-related complications such as cardiovascular disease and diabetic nephropathy, (iv) increase of serum TRAIL levels in diabetic patients after initiation of antidiabetic treatment and metabolic improvement. To explore the underlying mechanisms and provide mechanistic links between TRAIL and diabetes, a number of animal and in vitro studies have reported direct effects of TRAIL on several tissues involved in diabetes pathophysiology such as pancreatic islets, skeletal muscle, adipose tissue, liver, kidney, and immune and vascular cells. Residual controversy remains regarding the effects of TRAIL on adipose tissue homeostasis. Although the existing evidence is encouraging and paves the way for investigating TRAIL-related interventions in diabetic patients with cardiometabolic abnormalities, caution is warranted in the extrapolation of animal and in vitro data to the clinical setting, and further research in humans is imperative in order to uncover all aspects of the TRAIL-diabetes relationship and delineate its therapeutic implications in metabolic disease.     

Theoretical Perspectives and Empirical Facts on Water Sector Privatization: The Greek Case Against European and Global Trends

The scope of this paper is to investigate the Greek ‘path’ to water privatization and its possible interconnections with the ongoing restructuring of the water sector on an EU and a global level. The paper starts with a contemporary, spatially-sensitive analysis of the expanding role of water multinationals, by focusing on water supply operators of the southern EU. Afterwards, it highlights the peculiarities of the ‘Greek path’ to private sector participation by studying the two most important Greek water companies, in the cities of Athens and Thessaloniki respectively. As found, these companies have partially, though successfully, been transformed according to the rules of the ‘market-environmentalist’ paradigm. The state drives the privatization effort, while at the same time, insufficiently regulates the activity of both companies. Based on the Greek case, the paper discusses whether the analytical tools offered by a critical approach, the ‘accumulation-by-dispossession’ thesis, can better interpret changes in water companies of the ‘advanced-South’.