Molecular Pathway Reconstruction and Analysis of Disturbed Gene Expression in Depressed Individuals Who Died by Suicide

Molecular mechanisms behind the etiology and pathophysiology of major depressive disorder and suicide remain largely unknown. Recent molecular studies of expression of serotonin, GABA and CRH receptors in various brain regions have demonstrated that molecular factors may contribute to the development of depressive disorder and suicide behaviour. Here, we used microarray analysis to examine the expression of genes in brain tissue (frontopolar cortex) of individuals who had been diagnosed with major depressive disorder and died by suicide, and those who had died suddenly without a history of depression. We analyzed the list of differentially expressed genes using pathway analysis, which is an assumption-free approach to analyze microarray data. Our analysis revealed that the differentially expressed genes formed functional networks that were implicated in cell to cell signaling related to synapse maturation, neuronal growth and neuronal complexity. We further validated these data by randomly choosing (100 times) similarly sized gene lists and subjecting these lists to the same analyses. Random gene lists did not provide highly connected gene networks like those generated by the differentially expressed list derived from our samples. We also found through correlational analysis that the gene expression of control participants was more highly coordinated than in the MDD/suicide group. These data suggest that among depressed individuals who died by suicide, wide ranging perturbations of gene expression exist that are critical for normal synaptic connectively, morphology and cell to cell communication.     

Twintrons are not unique to the Euglena chloroplast genome: structure and evolution of a plastome cpn60 gene from a cryptomonad

Introns within introns (twintrons) are known only from the Euglena chloroplast genome. Twintrons are group II or III introns, into which another group II or III intron has been transposed. In this paper we describe a non-Euglena twintron structure within a plastid-encoded chaperone gene (cpn60) of the cryptomonad alga Pyrenomonas salina. In addition, the evolutionary relationships between members of the Cpn60 protein family are determined. Our findings permit the inclusion of cryptomonad plastomes in phylogenetic studies of intron evolution and present further evidence for the origin of modern plastids from a cyanobacterial ancestor.This paper is dedicated to Prof. Dr. Peter Sitte on the occasion of his 65th birthday     

Oral phosphatidylcholine pretreatment alleviates the signs of experimental rheumatoid arthritis

Introduction  

Phosphatidylcholine and phosphatidylcholine-derived metabolites exhibit anti-inflammatory properties in various stress conditions. We hypothesized that dietary phosphatidylcholine may potentially function as an anti-inflammatory substance and may decrease inflammatory activation in a chronic murine model of rheumatoid arthritis (collagen-induced arthritis).     

EPR-Spin Trapping and Flow Cytometric Studies of Free Radicals Generated Using Cold Atmospheric Argon Plasma and X-Ray Irradiation in Aqueous Solutions and Intracellular Milieu

Electron paramagnetic resonance (EPR)-spin trapping and flow cytometry were used to identify free radicals generated using argon-cold atmospheric plasma (Ar-CAP) in aqueous solutions and intracellularly in comparison with those generated by X-irradiation. Ar-CAP was generated using a high-voltage power supply unit with low-frequency excitation. The characteristics of Ar-CAP were estimated by vacuum UV absorption and emission spectra measurements. Hydroxyl (·OH) radicals and hydrogen (H) atoms in aqueous solutions were identified with the spin traps 5,5-dimethyl-1-pyrroline N-oxide (DMPO), 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (M₄PO), and phenyl N-t-butylnitrone (PBN). The occurrence of Ar-CAP-induced pyrolysis was evaluated using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) in aqueous solutions of DNA constituents, sodium acetate, and L-alanine. Human lymphoma U937 cells were used to study intracellular oxidative stress using five fluorescent probes with different affinities to a number of reactive species. The analysis and quantification of EPR spectra revealed the formation of enormous amounts of ·OH radicals using Ar-CAP compared with that by X-irradiation. Very small amounts of H atoms were detected whereas nitric oxide was not found. The formation of ·OH radicals depended on the type of rare gas used and the yield correlated inversely with ionization energy in the order of krypton > argon = neon > helium. No pyrolysis radicals were detected in aqueous solutions exposed to Ar-CAP. Intracellularly, ·OH, H₂O₂, which is the recombination product of ·OH, and OCl^- were the most likely formed reactive oxygen species after exposure to Ar-CAP. Intracellularly, there was no practical evidence for the formation of NO whereas very small amounts of superoxides were formed. Despite the superiority of Ar-CAP in forming ·OH radicals, the exposure to X-rays proved more lethal. The mechanism of free radical formation in aqueous solutions and an intracellular milieu is discussed.     

The role of protein kinases and protein phosphatases in the regulation of cardiac sarcoplasmic reticulum function

Summary Canine cardiac sarcoplasmic reticulum is phosphorylated by adenosine 3,5-monophosphate (cAMP)-dependent and by calcium · calmodulin-dependent protein kinases on a 27 000 proteolipid, called phospholamban. Both types of phosphorylation are associated with an increase in the initial rates of Ca²⁺ transport by SR vesicles which reflects an increased turnover of elementary steps of the calcium ATPase reaction sequence. The stimulatory effects of the protein kinases on the calcium pump may be reversed by an endogenous protein phosphatase, which can dephosphorylate both the CAMP-dependent and the calcium · calmodulin-dependent sites on phospholamban. Thus, the calcium pump in cardiac sarcoplasmic reticulum appears to be under reversible regulation mediated by protein kinases and protein phosphatases.     

Waste Treatment and Assessment of Long-Term Emissions (8pp)

Goal, Scope and Background The disposal phase of a product’s life cycle in LCA is often neglected or based on coarse indicators like ‘kilogram waste’. The goal of report No. 13 of the ecoinvent project (Doka 2003) is to create detailed Life Cycle Inventories of waste disposal processes. The purpose of this paper is to give an overview of the models behind the waste disposal inventories in ecoinvent, to present exemplary results and to discuss the assessment of long-term emissions. This paper does not present a particular LCA study. Inventories are compiled for many different materials and various disposal technologies. Considered disposal technologies are municipal incineration and different landfill types, including sanitary landfills, hazardous waste incineration, waste deposits in deep salt mines, surface spreading of sludges, municipal wastewater treatment, and building dismantling. The inventoried technologies are largely based on Swiss plants. Inventories can be used for assessment of the disposal of common, generic waste materials like paper, plastics, packaging etc. Inventories are also used within the ecoinvent database itself to inventory the disposal of specific wastes generated during the production phase. Inventories relate as far as possible to the specific chemical composition of the waste material (waste-specific burdens). Certain expenditures are not related to the waste composition and are inventoried with average values (process-specific burdens). Methods The disposal models are based on previous work, partly used in earlier versions of ecoinvent/ETH LCI data. Important improvements were the extension of the number of considered chemical elements to 41 throughout all disposal models and new landfill models based on field data. New inventories are compiled for waste deposits in deep salt mines and building material disposal. Along with the ecoinvent data and the reports, also Excel-based software tools were created, which allow ecoinvent members to calculate waste disposal inventories from arbitrary waste compositions. The modelling of long-term emissions from landfills is a crucial part in any waste disposal process. In ecoinvent long-term emissions are defined as emissions occurring 100 years after present. They are reported in separate emission categories. The landfill inventories include long-term emissions with a time horizon of 60’000 years after present. Results and Discussion As in earlier studies, the landfills prove to be generally relevant disposal processes, as also incineration and wastewater treatment processes produce landfilled wastes. Heavy metals tend to concentrate in landfills and are washed out to a varying degree over time. Long-term emissions usually represent an important burden from landfills. Comparisons between burdens from production of materials and the burdens from their disposal show that disposal has a certain relevance. Conclusion The disposal phase should by default be included in LCA studies. The use of a material not only necessitates its production, but also requires its disposal. The created inventories and user tools facilitate heeding the disposal phase with a similar level of detail as production processes. The risk of LCA-based decisions shifting burdens from the production or use phase to the disposal phase because of data gaps can therefore be diminished. Recommendation and Perspective Future improvements should include the modelling of metal ore refining waste (tailings) which is currently neglected in ecoinvent, but is likely to be relevant for metals production. The disposal technologies considered here are those of developed Western countries. Disposal in other parts of the World can differ distinctly, for logistic, climatic and economic reasons. The cross-examination of landfill models to LCIA soil fate models could be advantageous. Currently only chemical elements, like copper, zinc, nitrogen etc. are heeded by the disposal models. A possible extension could be the modelling of the behaviour of chemical compounds, like dioxins or other hydrocarbons.     

Simulated environmental effects of wetland restoration scenarios in a typical Canadian prairie watershed

Wetland conservation and restoration contribute to improved watershed functions through providing both water quantity benefits in terms of flood attenuation and water quality benefits such as retention of sediment and nutrients. However, it is important to quantify these environmental benefits for informed decision making. This study uses a “hydrologic equivalent wetland” concept in the Soil and Water Assessment Tool to examine the effects of various wetland restoration scenarios on stream flow and sediment at a watershed scale. The modeling system was applied to the 25,139 ha Broughton’s Creek watershed in western Manitoba in Canada. As a representative prairie watershed, the Broughton’s Creek watershed experienced historic wetland losses from 2,998 ha in 1968 to 2,379 ha in 2005. Modeling results showed that if wetlands in the Broughton’s Creek watershed can be restored to the 1968 level, the peak discharge and average sediment loading can be reduced by 23.4 and 16.9%, respectively at the watershed outlet. Based on wetland and stream drainage areas estimated by the model and empirical nutrient export coefficients, the corresponding water quality benefits in terms of reductions in total phosphorus and nitrogen loadings were estimated at 23.4%. The modeling results are helpful for designing effective watershed restoration strategies in the Broughton’s Creek watershed. The developed methodology can be also applied to other study areas for examining the environmental effects of wetland restoration scenarios.     

Chronic high blood flow potentiates shear stress-induced release of NO in arteries of aged rats

Aging impairs shear-stress-dependent dilation of arteries via increased superoxide production, decreased SOD activity, and decreased activation of endothelial nitric oxide (NO) synthase (eNOS). In the present study, we investigated whether chronic increases in shear stress, elicited by increases in blood flow, would improve vascular endothelial function of aged rats. To this end, second-order mesenteric arteries of young (6 mo) and aged (24 mo) male Fischer-344 rats were selectively ligated for 3 wk to elevate blood flow in a first-order artery [high blood flow (HF)]. An in vitro study was then conducted on first-order arteries with HF and normal blood flow (NF) to assess shear stress (1, 10, and 20 dyn/cm(2))-induced release of NO into the perfusate. In HF arteries of both age groups, shear stress-induced NO production increased significantly. In 24-mo-old rats, the reduced shear stress-induced NO production in NF arteries was normalized by HF to a level similar to that in NF arteries of 6-mo-old rats. The increased NO production in HF arteries of 24-mo-old rats was associated with increased shear stress-induced dilation, expression of eNOS protein, and shear stress-induced eNOS phosphorylation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, reduced shear stress-induced eNOS phosphorylation and vasodilation. Superoxide production decreased significantly in HF compared with NF arteries in 24-mo-old rats. The decreased superoxide production was associated with significant increases in CuZn-SOD and extracellular SOD protein expressions and total SOD activity. These results suggest that stimulation with chronic HF restores shear-stress-induced activation of eNOS and antioxidant ability in aged arteries.