Sexually Dimorphic Effect of the Val66Met Polymorphism of BDNF on Susceptibility to Alzheimer`s Disease: New Data and Meta-Analysis

Conflicting results have been reported as to whether genetic variations (Val66Met and C270T) of the brain-derived neurotrophic factor gene (RDNF) confer susceptibility to Alzheimer`s disease (AD). We genotyped these polymorphisms in a Japanese sample of 657 patients with AD and 525 controls, and obtained weak evidence of association for Val66Met (P = 0.063), but not for C270T. After stratification by sex, we found a significant allelic association between Val66Met and AD in women (P = 0.017), but not in men. To confirm these observations, we collected genotyping data for each sex from 16 research centers worldwide (4,711 patients and 4,537 controls in total). The meta-analysis revealed that there was a clear sex difference in the allelic association; the Met66 allele confers susceptibility to AD in women (odds ratio = 1.14, 95% CI 1.05-1.24, P = 0.002), but not in men. Our results provide evidence that the Met66 allele of BDNF has a sexually dimorphic effect on susceptibility to AD. (C) 2009 Wiley-Liss, Inc.

Chromosome polymorphism in Astyanax fasciatus (Teleostei, Characidae). 2-Chromosomal location of a satellite DNA

Studies about composition of repetitive sequences and their chromosomal location have been helpful to evolutionary studies in many distinct organisms. In order to keep on assessing the possible relationships among different cytotypes of Astyanax fasciatus (Teleostei, Characiformes) in the Mogi-Guacu River (Sao Paulo State, Brazil), C-banding, chromomycin A 3 staining, and fluorescent in situ hybridization with a repetitive DNA sequence (As51) isolated from Astyanax scabripinnis were performed in the present work. The constitutive heterochromatin was distributed in terminal regions on long arms of submetacentric, subtelocentric, and acrocentric chromosomes and in the terminal region on short arms of a pair of submetacentric chromosomes in both standard cytotypes. This latter heterochromatic site was also GC-rich, as revealed by chromomycin A(3) staining, corresponding to the nucleolar organizer region (NOR), as shown by previous studies. The sites of the satellite As51 DNA were located in terminal regions on long arms of several chromosomes. Some variant karyotypic forms, which diverge from the two standard cytotypes, also presented distinctive chromosomes carrying As51 satellite DNA. It is possible that the standard 2n = 46 cytotype represents an invader population in the Mogi-Guacu River able to interbreed with the resident standard 2n = 48 cytotype. Therefore, the variant karyotypes would be related to a possible viable offspring, where complementary chromosomal rearrangements could favor new locations of the satellite DNA analyzed. Copyright (C) 2008 S. Karger AG, Basel

Expression of TLR-4 and -2 in peripheral mononuclear cells in renal transplant patients with TLR-4 gene polymorphism

Introduction: TLR-4 has also been identified as a receptor for endogenous alarmins, which are increased post transplantation. TLR-4 has also been associated with a polymorphism that could impact graft outcome. Objective: To assess the expression of TLR-4 in kidney transplant patients carrying or not a polymorphism. Methods: TLR-4 polymorphism (A299G/T399I) was studied in 200 renal transplant patients. Healthy volunteers were also enrolled as control group. The polymorphism analysis was performed using restriction enzymes technique (RFLP). Functionality of TLR-4 polymorphism was assessed in samples from controls by quantification of TNF-alpha after LPS stimulus. TLR-4 and -2 expressions were also analyzed by flow cytometry. Results: TLR-4 polymorphism was present in 8.5% of renal transplant patients. This polymorphism was associated with impairment in TNF-alpha secretion. In general, in renal transplant patients, TLR-4 expression in monocytes and in neutrophils was lower than in health volunteers. TLR-2 and TLR-4 expressions in healthy volunteers with A299G/T399I TLR-4 polymorphism was higher than in wild-type genotype healthy volunteers (p<0.01 and p<0.05, respectively), and also higher than A299G/T399I TLR-4 polymorphism renal transplant patients (p<0.05). TLR-2 expression on neutrophils in wild-type genotype renal transplant patients was higher compared to wild-type genotype healthy volunteers, and was also higher in relation to A299G/T399I kidney transplanted patients (p<0.01). Conclusion: Stable renal transplant patients with TLR-4 polymorphism have a lower expression of TLR-4 and TLR-2 receptors in peripheral mononuclear cells, which ultimately indicate a less responsiveness for alarmins. (C) 2010 Elsevier B.V. All rights reserved.

Association of complement factor H Y402H polymorphism and age-related macular degeneration in Brazilian patients

Purpose: The aim of this study was investigate the association between complement Factor H polymorphism (Y402H) and age-related macular degeneration (AMD) in Brazilian patients. Methods: Patients with AMD aged 50 or more and age-matched healthy controls were enrolled in the study. Genomic DNA was isolated from leucocytes of patients and controls; the Y402H polymorphism of complement Factor H gene (CFH) was determined by polymerase chain reaction directed sequencing. Results: The frequency of 1277C allele of Factor H was 56.30% in patients with AMD compared with 36.51% in controls (p-value = 0.001). The genotypic distribution differed significantly between the two groups (1277CC 36.98%, 1277CT 38.65% and 1277TT 24.37% for AMD group; 1277CC 13.16%, 1277CT 46.71% and 1277TT 40.13% for controls, p-value = 0.001). The odds ratio for patients with AMD carrying only one 1277C allele was 1.36 and for those carrying two 1277C alleles was 4.63, when compared to the control group. Conclusions: These results suggest the Y402H polymorphism of CFH is a risk factor to the development of AMD in Brazilian patients. This is in accordance with findings from the majority of previous study population in Europe and North American.

Improved renal function after kidney transplantation is associated with heme oxygenase-1 polymorphism

Heme oxygenase-1 (HO-1) has a microsatellite polymorphism based on the number of guanosine-thymidine nucleotide repeats (GT) repeats that regulates expression levels and could have an impact on organ survival post-injury. We correlated HO-1 polymorphism with renal graft function. The HO-1 gene was sequenced (N = 181), and the allelic repeats were divided into subclasses: short repeats (S) (< 27 repeats) and long repeats (L) (>= 27 repeats). A total of 47.5% of the donors carried the S allele. The allograft function was statistically improved six months, two and three yr after transplantation in patients receiving kidneys from donors with an S allele. For the recipients carrying the S allele (50.3%), the allograft function was also better throughout the follow-up, but reached statistical significance only three yr after transplantation (p = 0.04). Considering only those patients who had chronic allograft nephropathy (CAN; 74 of 181), allograft function was also better in donors and in recipients carrying the S allele, two and three yr after transplantation (p = 0.03). Recipients of kidney transplantation from donors carrying the S allele presented better function even in the presence of CAN.

An interleukin-1 beta (IL-1 beta) single-nucleotide polymorphism at position 3954 and red complex periodontopathogens independently and additively modulate the levels of IL-1 beta in diseased periodontal tissues

Inflammatory cytokines such as interieukin-1 beta (IL-1 beta) are involved in the pathogenesis of periodontal diseases. A high individual variation in the levels of IL-10 mRNA has been verified, which is possibly determined by genetic polymorphisms and/or by the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans. In this study, we investigated the role of an IL-10 promoter single-nucleotide polymorphism at position 3954 [IL-1 beta(3954) SNP] and the presence of the periodontopathogens in the determination of the IL-1 beta levels in the periodontal tissues of nonsmoking chronic periodontitis (CP) patients (n = 117) and control (C) subjects in = 175) and the possible correlations with the clinical parameters of the disease. IL-1 beta(3954) SNP was investigated by restriction fragment length polymorphism, while the IL-1 beta levels and the presence of the periodontopathogens were determined by real-time PCR. Similar frequencies of IL-1 beta(3954) SNP were found in the C and CP groups, in spite of a trend toward a higher incidence of T alleles in the CP group. The IL-1 beta (3954) SNP CT and TT genotypes, as well as P. gingivalis, T. forsythia, and T. denticola, were associated with higher IL-1 beta levels and with higher values of the clinical parameters of disease severity. Concomitant analyses demonstrate that IL-1 beta(3954) and the red complex periodontopathogens were found to independently and additively modulate the levels of IL-1 beta in periodontal tissues. Similarly, the concurrent presence of both factors was associated with increased scores of disease severity. IL-1 beta(3954) genotypes and red complex periodontopathogens, individually and additively, modulate the levels of IL-1 beta in the diseased tissues of nonsmoking CP patients and, consequently, are potentially involved in the determination of the disease outcome.

Tumor necrosis factor-alpha-308G/A single nucleotide polymorphism and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased periodontal tissues

Background and Objective: Inflammatory cytokines such as tumor necrosis factor-alpha are involved in the pathogenesis of periodontal diseases. A high between-subject variation in the level of tumor necrosis factor-alpha mRNA has been verified, which may be a result of genetic polymorphisms and/or the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola (called the red complex) and Aggregatibacter actinomycetemcomitans. In this study, we investigated the effect of the tumor necrosis factor-alpha (TNFA) -308G/A gene polymorphism and of periodontopathogens on the tumor necrosis factor-alpha levels in the periodontal tissues of nonsmoking patients with chronic periodontitis (n = 127) and in control subjects (n = 177). Material and Methods: The TNFA-308G/A single nucleotide polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism analysis, whereas the tumor necrosis factor-alpha levels and the periodontopathogen load were determined using real-time polymerase chain reaction. Results: No statistically significant differences were found in the frequency of the TNFA-308 single nucleotide polymorphism in control and chronic periodontitis groups, in spite of the higher frequency of the A allele in the chronic periodontitis group. The concomitant analyses of genotypes and periodontopathogens demonstrated that TNFA-308 GA/AA genotypes and the red-complex periodontopathogens were independently associated with increased levels of tumor necrosis factor-alpha in periodontal tissues, and no additive effect was seen when both factors were present. P. gingivalis, T. forsythia and T. denticola counts were positively correlated with the level of tumor necrosis factor-alpha. TNFA-308 genotypes were not associated with the periodontopathogen detection odds or with the bacterial load. Conclusion: Our results demonstrate that the TNFA-308 A allele and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased tissues of nonsmoking chronic periodontitis patients and consequently are potentially involved in determining the disease outcome.

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people

The polymorphisms of endothelial nitric oxide synthase (eNOS) are associated with reduced eNOS activity. Aerobic exercise training (AEX) may influence resting nitric oxide (NO) production, oxidative stress and blood pressure. The purpose of this study was to investigate the effect of AEX on the relationship among blood pressure, eNOS gene polymorphism and oxidative stress in pre-hypertensive older people. 118 pre-hypertensive subjects (59 +/- A 6 years) had blood samples collected after a 12 h overnight fast for assessing plasma NO metabolites (NOx) assays, thiobarbituric acid reactive substances (T-BARS) and superoxide dismutase activity (ecSOD). eNOS polymorphism (T-786C and G-894T) was done by standard PCR methods. All people were divided according to the genotype results (G1: TT/GG, G2: TT/GT + TT, G3: TC + CC/GG, G4: TC + CC/GT + TT). All parameters were measured before and after 6 months of AEX (70% of VO(2 max)). At baseline, no difference was found in systolic and diastolic blood pressure, ecSOD and T-BARS activity. Plasma NOx levels were significantly different between G1 (19 +/- A 1 mu M) and G4 (14.2 +/- A 0.6 mu M) and between G2 (20.1 +/- A 1.7 mu M) and G4 (14.2 +/- A 0.6 mu M). Therefore, reduced NOx concentration in G4 group occurred only when the polymorphisms were associated, suggesting that these results are more related to genetic factors than NO-scavenging effect. After AEX, the G4 increased NOx values (17.2 +/- A 1.2 mu M) and decreased blood pressure. G1, G3 and G4 decreased T-BARS levels. These results suggest the AEX can modulate the NOx concentration, eNOS activity and the relationship among eNOS gene polymorphism, oxidative stress and blood pressure especially in C (T-786C) and T (G-894T) allele carriers.

Conformational Polymorphism in Racemic Crystals of the Diuretic Drug Chlortalidone

Chlortalidone (HIGROTON) is a diuretic drug widely used in antihypertensive therapy. Thus far, only two solid-state polymorphs of chlortalidone have been reported. We elucidated the structure of chlortalidone form I and a new polymorph. This new phase, namely, chlortalidone form III, was also entirely characterized. It was possible to conclude that it is a conformer with a different orientation of the chlorobenzenesulfonamide moiety. Compared to form I, it has a rotation of about 90 degrees on the axis of the C-C bond bridging the substituted phenyl and isoindolinyl rings. This conformational feature is related to the crystal packing patterns of the chlortalidone forms. Furthermore, certain intermolecular hydrogen bonds are present in both polymorphs, giving rise to ribbons with chlortalidone enantiomers alternately placed into them. The chlortalidone form I and form III crystallize in the triclinic space group P (1) over bar as racemic mixtures. Additional conformational details also differentiate the chlortalidone conformers. Slight twists on the isoindolinyl and sulfamyl groups exist. Considering all structural relationships, the fingerprint plots derived from the Hirshfeld surfaces exhibited the characteristics of the chlortalidone form I and form III crystal structures.

eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity

Statins have pleiotropic effects, including endothelial nitric oxide synthase (eNOS) upregulation and increased nitric oxide formation, which can be modulated by a genetic polymorphism in the promoter region of the eNOS gene (T-786C). Here, we report our investigation of whether this polymorphism modulates the effects of atorvastatin on the fluidity of erythrocyte membranes. We genotyped 200 healthy subjects (males, 18-60 years of age) and then randomly selected 15 of these with the TT genotype and 15 with the CC genotype to receive placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell membrane fluidity was evaluated by electron paramagnetic resonance (EPR) and spin-labeling method. The EPR spectra were registered on a VARIAN-E4 spectrometer. Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol were determined in the erythrocytes. Atorvastatin reduced membrane fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P > 0.05). While no significant differences were found in plasma membrane cholesterol concentrations, higher TBA-RS concentrations were found in the CC subjects than in the TT subjects (P < 0.05). These findings suggest that a short treatment with atorvastatin is disadvantageous to subjects with the CC genotype for the T-786C polymorphism compared to those with TT genotype, at least in terms of the hemorheological properties of erythrocytes.

Removal of Zn(2+) from Electroplating Wastewater Using Modified Wood Sawdust and Sugarcane Bagasse

This paper describes the preparation of new adsorbents derived from sugarcane bagasse and wood sawdust (Manilkara sp.) to remove zinc (II) ions from electroplating wastewater. The first part deals with the chemical modification of sugarcane bagasse and wood sawdust, using succinic anhydride to introduce carboxylic acid functions into the material. The obtained materials (modified sugarcane bagasse MB2 and modified wood sawdust MS2) were then characterized by infrared spectroscopy (IR) and used in adsorption experiments. The adsorption experiments evaluates Zn(2+) removal from aqueous single metal solution and real electroplating wastewater on both batch and continuous experiments using fixed-bed columns prepared in laboratorial scale with the obtained adsorbents. Adsorption isotherms were then developed using Langmuir model and the Thomas kinetic model. The calculated Zn(2+) adsorption capacities were found to be 145 mg/g for MS2 and 125 mg/g for MB2 in single metal aqueous solution, whereas for the industrial wastewater these values were 61 mg/g for MS2 and 55 mg/g for MB2.

The value of a saved tree : The lifecycle of CO2-emissions associated with the combination of printing paper and electricity production of wood in the U.S. and Sweden

The pulp- and paper production is a very energy intensive industry sector. Both Sweden and the U.S. are major pulpandpaper producers. This report examines the energy and the CO2-emission connected with the pulp- and paperindustry for the two countries from a lifecycle perspective.New technologies make it possible to increase the electricity production in the integrated pulp- andpaper mill through black liquor gasification and a combined cycle (BLGCC). That way, the mill canproduce excess electricity, which can be sold and replace electricity produced in power plants. In thisprocess the by-products that are formed at the pulp-making process is used as fuel to produce electricity.In pulp- and paper mills today the technology for generating energy from the by-product in aTomlinson boiler is not as efficient as it could be compared to the BLGCC technology. Scenarios havebeen designed to investigate the results from using the BLGCC technique using a life cycle analysis.Two scenarios are being represented by a 1994 mill in the U.S. and a 1994 mill in Sweden.The scenariosare based on the average energy intensity of pulp- and paper mills as operating in 1994 in the U.S.and Sweden respectively. The two other scenarios are constituted by a »reference mill« in the U.S. andSweden using state-of-the-art technology. We investigate the impact of varying recycling rates and totalenergy use and CO2-emissions from the production of printing and writing paper. To economize withthe wood and that way save trees, we can use the trees that are replaced by recycling in a biomassgasification combined cycle (BIGCC) to produce electricity in a power station. This produces extra electricitywith a lower CO2 intensity than electricity generated by, for example, coal-fired power plants.The lifecycle analysis in this thesis also includes the use of waste treatment in the paper lifecycle. Both Sweden and theU.S. are countries that recycle paper. Still there is a lot of paper waste, this paper is a part of the countries municipalsolid waste (MSW). A lot of the MSW is landfilled, but parts of it are incinerated to extract electricity. The thesis hasdesigned special scenarios for the use of MSW in the lifecycle analysis.This report is studying and comparing two different countries and two different efficiencies on theBLGCC in four different scenarios. This gives a wide survey and points to essential parameters to specificallyreflect on, when making assumptions in a lifecycle analysis. The report shows that there arethree key parameters that have to be carefully considered when making a lifecycle analysis of wood inan energy and CO2-emission perspective in the pulp- and paper mill in the U.S. and in Sweden. First,there is the energy efficiency in the pulp- and paper mill, then the efficiency of the BLGCC and last theCO2 intensity of the electricity displaced by BIGCC or BLGCC generatedelectricity. It also show that with the current technology that we havetoday, it is possible to produce CO2 free paper with a waste paper amountup to 30%. The thesis discusses the system boundaries and the assumptions.Further and more detailed research, including amongst others thesystem boundaries and forestry, is recommended for more specificanswers.

Vedegenskaper i härskande och behärskade granar vid Remingstorp : Wood properties in dominant and sub-dominant trees of Norway spruce at Remingstorp

Variation in wood properties for Picea abies trees and logs of different dimensions has been studied at two sites in southern Sweden of different site quality class. Trees have been classified as dominant or sub-dominant, according to their height. Log and board grades were classified and strength grade of boards, basic density and annual ring width measured. A similar study made on four northern sites was used as reference material.Sub-dominant trees were of superior quality in comparison to dominant trees, when classified by log and board grades or strength grading. Differences were accentuated for the second log where the sub-dominant trees had superior strength and low amount of boards with coarse branches. The results correspond well to those from the northern region, Jämtland. The classifica¬tion of boards as well as bending strength indicated superior properties on timber from northern sites even though the basic density was similar.

Methodology for identifying parameters for the TRNSYS model Type 210 -wood pellet stoves and boilers

This report describes a method how to perform measurements on boilers and stoves and how to identify parameters from the measurements for the boiler/stove-model TRNSYS Type 210. The model can be used for detailed annual system simulations using TRNSYS. Experience from measurements on three different pellet stoves and four boilers were used to develop this methodology. Recommendations for the set up of measurements are given and the re-quired combustion theory for the data evaluation and data preparation are given. The data evalua-tion showed that the uncertainties are quite large for the measured flue gas flow rate and for boilers and stoves with high fraction of energy going to the water jacket also the calculated heat rate to the room may have large uncertainties. A methodology for the parameter identification process and identified parameters for two different stoves and three boilers are given. Finally the identified models are compared with measured data showing that the model generally agreed well with meas-ured data during both stationary and dynamic conditions.

Emissions from realistic operation of residential wood pellets heating systems

Emissions from residential combustion appliances vary significantly depending on the firing behaviours and combustion conditions, in addition to combustion technologies and fuel quality. Although wood pellet combustion in residential heating boilers is efficient, the combustion conditions during start-up and stop phases are not optimal and produce significantly high emissions such as carbon monoxide and hydrocarbon from incomplete combustion. The emissions from the start-up and stop phases of the pellet boilers are not fully taken into account in test methods for ecolabels which primarily focus on emissions during operation on full load and part load. The objective of the thesis is to investigate the emission characteristics during realistic operation of residential wood pellet boilers in order to identify when the major part of the annual emissions occur. Emissions from four residential wood pellet boilers were measured and characterized for three operating phases (start-up, steady and stop). Emissions from realistic operation of combined solar and wood pellet heating systems was continuously measured to investigate the influence of start-up and stop phases on total annual emissions. Measured emission data from the pellet devices were used to build an emission model to predict the annual emission factors from the dynamic operation of the heating system using the simulation software TRNSYS. Start-up emissions are found to vary with ignition type, supply of air and fuel, and time to complete the phase. Stop emissions are influenced by fan operation characteristics and the cleaning routine. Start-up and stop phases under realistic operation conditions contribute 80 – 95% of annual carbon monoxide (CO) emission, 60 – 90% total hydrocarbon (TOC), 10 – 20% of nitrogen oxides (NO), and 30 – 40% particles emissions. Annual emission factors from realistic operation of tested residential heating system with a top fed wood pelt boiler can be between 190 and 400 mg/MJ for the CO emissions, between 60 and 95 mg/MJ for the NO, between 6 and 25 mg/MJ for the TOC, between 30 and 116 mg/MJ for the particulate matter and between 2x10-13 /MJ and 4x10-13 /MJ for the number of particles. If the boiler has the cleaning sequence with compressed air such as in boiler B2, annual CO emission factor can be up to 550 mg/MJ. Average CO, TOC and particles emissions under realistic annual condition were greater than the limits values of two eco labels. These results highlight the importance of start-up and stop phases in annual emission factors (especially CO and TOC). Since a large or dominating part of the annual emissions in real operation arise from the start-up and stop sequences, test methods required by the ecolabels should take these emissions into account. In this way it will encourage the boiler manufacturers to minimize annual emissions. The annual emissions of residential pellet heating system can be reduced by optimizing the number of start-ups of the pellet boiler. It is possible to reduce up to 85% of the number of start-ups by optimizing the system design and its controller such as switching of the boiler pump after it stops, using two temperature sensors for boiler ON/OFF control, optimizing of the positions of the connections to the storage tank, increasing the mixing valve temperature in the boiler circuit and decreasing the pump flow rate. For 85 % reduction of start-ups, 75 % of CO and TOC emission factors were reduced while 13% increase in NO and 15 % increase in particle emissions was observed.