In a large Scottish pedigree, disruption of the gene coding for DISC1 clearly segregates with major depression, schizophrenia and related mental conditions. Thus, study of DISC1 may provide a clue to understand the biology of major mental illness. A neuropeptide precursor VGF has potent antidepressant effects and has been reportedly associated with bipolar disorder. Here we show that DISC1 knockdown leads to a reduction of VGF, in neurons. VGF is also downregulated in the cortices from sporadic cases with major mental disease. A positive correlation of VGF single-nucleotide polymorphisms (SNPs) with social anhedonia was also observed. We now propose that VGF participates in a common pathophysiology of major mental disease.
The activities of 11 C-8-O-acyl and alkyl analogs of the antiprotozoal sesquiterpene lactone, incomptine A (1) against Entamoeba histolytica and Giardia lamblia, were determined. Here, the effects of different lengths and amounts of branching of the acyl and alkyl groups on the antiprotozoal activity of the synthesized incomptine A-analogs are reported.
Biohydrogen is a sustainable form of energy as it can be produced from organic waste through fermentation processes involving dark fermentation and photofermentation. Very often biohydrogen is included as a part of biorefinery approaches, which reclaim organic wastes that are abundant sources of renewable and low cost substrate that can be efficiently fermented by microorganisms. The aim of this work was to critically assess selected bioenergy alternatives from organic solid waste, such as biohydrogen and bioelectricity, to evaluate their relative advantages and disadvantages in the context of biorefineries, and ?nally to indicate the trends for future research and development. Biorefining is the sustainable processing of biomass into a spectrum of marketable products, which means: energy, materials, chemicals, food and feed. Dark fermentation of organic wastes could be the beach-head of complete biorefineries that generate biohydrogen as a first step and could significantly influence the future of solid waste management. Series systems show a better efficiency than one-stage process regarding substrate conversion to hydrogen and bioenergy. The dark fermentation also produces fermented by-products (fatty acids and solvents), so there is an opportunity for further combining with other processes that yield more bioenergy. Photoheterotrophic fermentation is one of them: photosynthetic heterotrophs, such as non-sulfur purple bacteria, can thrive on the simple organic substances produced in dark fermentation and light, to give more H2. Effluents from photoheterotrophic fermentation and digestates can be processed in microbial fuel cells for bioelectricity production and methanogenic digestion for methane generation, thus integrating a diverse block of bioenergies. Several digestates from bioenergies could be used for bioproducts generation, such as cellulolytic enzymes and saccharification processes, leading to ethanol fermentation (another bioenergy), thus completing the inverse cascade. Finally, biohydrogen, biomethane and bioelectricity could contribute to significant improvements for solid organic waste management in agricultural regions, as well as in urban areas.
Two new 5,10-seco-neo-clerodanes, salvimicrophyllins A and B (1 and 2), and two new neo-clerodanes, salvimicrophyllins C and D (3 and 4), were isolated from the leaves and flowers of Salvia microphylla. The structures of these compounds were elucidated mainly by analysis of their NMR spectroscopic and mass spectrometric data. The relative configurations of the salvimicrophyllins were determined by analysis of NOESY spectra and ECD curves, and the relative configuration of compound 2 was confirmed by single-crystal X-ray diffraction crystallography.
Six new hydroxyclerodanes (1-6), named sepulturins A-F, and four known diterpenes were isolated from the leaves of Salvia shannoni. The structures of these compounds were established by extensive analysis of their NMR and MS spectroscopic data. The relative configurations of compounds 1 and 2 were determined by NOESY experiments and were confirmed by single-crystal X-ray diffraction studies. All of the isolated diterpenes possess tertiary OH groups. The structure of infuscatin (7), a clerodane previously isolated from S. infuscata, was revised. Cytotoxic, antiprotozoal, and anti-inflammatory activities of these compounds were evaluated.
Microphyllandiolide (1), an unprecedented rearranged clerodane-type diterpene with a 9/3 bicyclic ring system, was isolated from the aerial parts of Salvia microphylla Kunth. Its structure was elucidated by analysis of its spectroscopic data and confirmed by single crystal X-ray diffraction analysis. A possible biogenesis for microphyllandiolide (1) is proposed.
Entamoeba histolytica is the causative agent of human amoebiasis, which mainly affects developing countries. Although several drugs are effective against E. histolytica trophozoites, the control of amoebiasis requires the development of new and better alternative therapies. Medicinal plants have been the source of new molecules with remarkable antiprotozoal activity. Incomptine A isolated from Decachaeta incompta leaves, is a sesquiterpene lactone of the heliangolide type which has the major in vitro activity against E. histolytica trophozoites. However the molecular mechanisms involved in its antiprotozoal activity are still unknown. Using a proteomic approach based on two-dimensional gel electrophoresis and mass spectrometry (ESI-MS/MS) analysis, we evidenced that 21 E. histolytica proteins were differentially expressed in response to incomptine A treatment. Notably, three glycolytic enzymes, namely enolase, pyruvate:ferredoxin oxidoreductase and fructose-1,6-biphosphate aldolase, were down-regulated. Moreover, ultrastructural analysis of trophozoites through electronic microscopy showed an increased number of glycogen granules. Taken together, our data suggested that incomptine A could affect E. histolytica growth through alteration of its energy metabolism.
Hydrogen is a valuable clean energy source, and its production by biological processes is attractive and environmentally sound and friendly. In México 5 million tons/yr of agroindustrial wastes are generated; these residues are rich in fermentable organic matter that can be used for hydrogen production. On the other hand, batch, intermittently vented, solid substrate fermentation of organic waste has attracted interest in the last 10 years. Thus the objective of our work was to determine the effect of initial total solids content and initial pH on H2 production in batch fermentation of a substrate that consisted of a mixture of sugarcane bagasse, pineapple peelings, and waste activated sludge. The experiment was a response surface based on 2(2) factorial with central and axial points with initial TS (15-35%) and initial pH (6.5-7.5) as factors. Fermentation was carried out at 35 °C, with intermittent venting of minireactors and periodic flushing with inert N2 gas. Up to 5 cycles of H2 production were observed; the best treatment in our work showed cumulative H2 productions (ca. 3 mmol H2/gds) with 18% and 6.65 initial TS and pH, respectively. There was a significant effect of TS on production of hydrogen, the latter decreased with initial TS increase from 18% onwards. Cumulative H2 productions achieved in this work were higher than those reported for organic fraction of municipal solid waste (OFMSW) and mixtures of OFMSW and fruit peels waste from fruit juice industry, using the same process. Specific energetic potential due to H2 in our work was attractive and fell in the high side of the range of reported results in the open literature. Batch dark fermentation of agrowastes as practiced in our work could be useful for future biorefineries that generate biohydrogen as a first step and could influence the management of this type of agricultural wastes in México and other countries and regions as well.
The aim of this study was to estimate genetic and environmental influences on the longitudinal evolution of leisure-time physical activity habits from adolescence to young adulthood. Data were gathered at four time points, at mean ages 16.2, 17.1, 18.6, and 24.5 years. At baseline, the sample comprised 5,216 monozygotic and dizygotic twins, born 1975-1979, and, at the last follow-up point, of 4,531 monozygotic and dizygotic twins. Physical activity volume was assessed as frequency of leisure-time physical activity and participants were categorized into three groups: inactive, moderately active, and active. Genetic and environmental influences were estimated using a multivariate, longitudinal Cholesky decomposition with a multifactorial liability threshold approach. The results suggest that, in both sexes the heritability of leisure-time physical activity remained moderate (~43-52%) during adolescence, declining to ~30% in young adulthood. Shared environmental influences increased from adolescence (~18-26%) to young adulthood (43% in men and 49% in women). Specific environmental influences remained relatively stable during the total follow-up (~20-30%). New genetic, shared, and specific environmental influences at every follow-up point were suggested by the low correlations across occasions. In conclusion, the study demonstrated gender differences in genetic influences in the evolution of leisure-time physical activity habits from adolescence to young adulthood. However, shared environmental influences, especially in women, were crucial in explaining longitudinal changes in leisure-time physical activity. These outcomes emphasize the need of gender-specific measures to promote physical activity habits during young adulthood.
Twin registries around the globe have collected DNA samples from large numbers of monozygotic and dizygotic twins. The twin sample collections are frequently used as controls in disease-specific studies together with non-twins. This approach is unbiased under the hypothesis that twins and singletons are comparable in terms of allele frequencies; i.e. there are no genetic variants associated with being a twin per se. To test this hypothesis we performed a genome-wide association study comparing the allele frequency of 572,352 single nucleotide polymorphisms (SNPs) in 1,413 monozygotic (MZ) and 5,451 dizygotic (DZ) twins with 3,720 healthy singletons. Twins and singletons have been genotyped using the same platform. SNPs showing association with being a twin at P-value < 1 × 10(-5) were selected for replication analysis in 1,492 twins (463 MZ and 1,029 DZ) and 1,880 singletons from Finland. No SNPs reached genome-wide significance (P-value < 5 × 10(-8)) in the main analysis combining MZ and DZ twins. In a secondary analysis including only DZ twins two SNPs (rs2033541 close to ADAMTSL1 and rs4149283 close to ABCA1) were genome-wide significant after meta-analysis with the Finnish population. The estimated proportion of variance on the liability scale explained by all SNPs was 0.08 (P-value=0.003) when MZ and DZ were considered together and smaller for MZ (0.06, P-value=0.10) compared to DZ (0.09, P-value=0.003) when analyzed separately. In conclusion, twins and singletons can be used in genetic studies together with general population samples without introducing large bias. Further research is needed to explore genetic variances associated with DZ twinning.
BMI increases progressively from adolescence to young adulthood. The aims of the present study were firstly, to investigate the extent to which genetic and environmental influences account for differences in BMI trajectories during this period, and secondly to examine whether boys and girls show divergences in these influences, as their BMI normally start differing across adolescence. The study sample consisted of 4,915 monozygotic and like- and unlike-sex dizygotic twins, born between 1975 and 1979. Data on BMI was gathered when twins were on average 16.1, 17.1, 18.6 and 24.4 years old. Genetic and environmental influences on the BMI trajectories were modeled using a latent growth curve approach. The results showed that the heritability of BMI decreased slightly after the adolescence period, from ? 80 to 70%. BMI transition from adolescence to young adulthood was best described by a quadratic trajectory that was highly accounted (61.7-86.5%) for by additive genetic influences. Genetic influences on BMI level showed a low correlation with those on the trend in BMI with age indicating that different sets of genes underlie the change of BMI during this period. Importantly, the analyses also evidenced that different genetic and environmental influences may underlie boys and girls evolution. In conclusion, our results suggested specific genetic influences accounting for the BMI rate-of-change from adolescence to young adulthood. This indicates that the specific genes behind BMI level may not be the same as the genes affecting BMI change which should be taken into account in further efforts to identify these genes.
Animal studies have suggested that angiopoietin-like 4 (Angptl4) regulates adiposity through central and peripheral mechanisms. The aim of this study was to investigate whether serum concentration and adipose tissue expression of Angptl4 are associated with obesity-related parameters in humans. Altogether, 75 dizygotic (DZ) and 46 monozygotic (MZ) twin pairs were studied, from the FinnTwin12 and FinnTwin16 cohorts. Among the MZ pairs, 21 were discordant for body mass index (BMI) (intra-pair BMI-difference >2.5 kg/m², age 23-33 years). Serum Angptl4 (s-Angptl4) levels were measured by ELISA, and adipose tissue gene expression was analyzed by genome-wide transcript profiling. In MZ twin pairs discordant for BMI, s-Angptl4 and adipose tissue ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P = 0.04 and P = 0.03, respectively) in obese twins as compared with their nonobese cotwins. In all twins, intra-pair differences in s-Angptl4 levels were inversely correlated with intra-pair differences in BMI (r = -0.27, P = 0.003). In individual MZ twins, at-ANGPTL4 expression was inversely correlated with BMI (r = -0.44, P = 0.001) and positively correlated with at-LIPE (r = 0.24, P = 0.01) and at-ABHD5 (r = 0.41, P = 0.005) expression. Our results demonstrated that variation in Angptl4 concentration was only modestly accounted for by genetic factors and suggest a role for Angptl4 in acquired obesity in humans.
The clam Megapitaria squalida is a fishing resource with increasing importance in Northwestern Mexico. Nevertheless, this fishery has shown important variations that could be related to environmental factors. To assess this, monthly landings of M. squalida were analyzed during 2002-2005 for Bahía de La Paz, B.C.S., and were related with monthly time series of sea surface temperature, derived from MODIS-Aqua Sensor. The results showed a positive and significant relationship between sea surface temperature and clam landings. The likely impact of anomalous conditions of sea temperature on this resource is discussed.
Emerging as an important metabolic regulator, fibroblast growth factor 21 (FGF21) has gained considerable interest in diabetes and obesity research. The circulating FGF21 concentration is fairly low in normal individuals, but elevated hormone levels may associate with obesity. The determining factors of FGF21 levels in humans are not clear.
The purpose of this study was to examine changes in the contribution of genetic and environmental influences to leisure time physical activity among male and female twins over a 6-year follow-up. At baseline the sample comprised 4,280 monozygotic and 9,276 dizygotic twin individuals, and at follow-up 4,383 monozygotic and 9,439 dizygotic twin individuals. Participants were aged 18-54 years at baseline. Genetic modeling results showed that genetic influences on leisure time physical activity declined from baseline (44%) to follow-up (34%). Most of the genetic influences identified at baseline were present at followup (r(g) = 0.72). Specific environmental influences increased from baseline (56%) to follow-up (66%) while at follow-up new environmental time-specific influences were observed (r(e) = 0.23). The model with sex differences showed a higher estimate of genetic influences for men than women both at baseline (men 47% vs. women 42%) and at follow-up (men 38% vs. women 31%). The additive genetic correlation for this phenotype was greater for men (r(g) = 0.79) than women (r(g) = 0.64). The specific environmental influences were corresponding; at baseline men 53% and women 56% and at follow-up men 62 % and women 69%. The environmental correlations between the two time points were similar for men (r(e)= 0.21) and for women (r(e)= 0.24). In conclusion, in a sample of healthy twins most of the genetic influences on leisure time physical activity expressed at baseline were present at 6 years of follow-up. New specific environmental factors underlying follow-up leisure time physical activity were observed.
Both left ventricular hypertrophy (LVH) and repolarization phase (RP) are known to be attributable to genetic influences, but less is known whether they share same genetic influences. The aim of this study was to investigate to what extent individual differences in electrocardiographic (ECG) LVH and RP are explained by genetic and environmental influences and whether these influences are shared between these two traits.
Weight gain through middle age is a common phenomenon that increases the risk for different types of metabolic diseases and functional limitations later in life. This study examined genetic and environmental influences on the evolution of body mass index (BMI) in women from middle to old age. BMI was evaluated in 102 monozygotic and 114 dizygotic pairs of twin sisters from the year 1975, when they were 42.6 +/- 3.4 years-old, and thereafter in 1981, 1990, 2001 and 2004, in a total 29-year follow-up period. We examined genetic and environmental influences explaining BMI overall level and its rate of change using a latent growth modeling approach. The results showed that mean (+/-SD) BMI increased from 24.1 +/- 3.1 to 28.2 +/- 5.1 kg/m(2) during the 29-year period. The heritability of BMI showed a consistent increment across occasions, from 54% in 1975, to 72% in 2004. Genetic influences accounted for both overall BMI level (60%) and BMI rate of change (64%). Genetic and environmental correlations between BMI level and rate of change were: r(g) = 0.40 and r(e) = -0.24, respectively. We conclude that in relatively healthy women, genes affecting level of BMI may differ from those affecting change in BMI with age. These results provide a basis for identifying genetic variants for change in BMI.
The purpose of this study was to examine how resting electrocardiographic (ECG) and other clinical variables, which can be included in a routine clinical examination, predict walking ability in older women. Three hundred and twenty women (63-75 years) without overt cardiac diseases and apparent mobility limitations were studied. Measurements performed were clinical examination (standard 12-lead resting ECG, assessment of physical activity level, presence of chronic diseases, use of beta-blockers, body mass index (BMI), ability to squat, resting blood pressure) and six-minute walking test. Participants walked 533+/-75 m in the six-minute walking test. The best electrocardiographic predictors of long walking distance were high TV(5) and TII, but their explanation rates were small (4.5% and 3.8%, respectively). In hypertensive participants (systolic blood pressure=SBP> or =160 mmHg), the respective values were 9.3% and 5.8%. The best predictors of long walking distance were ability to squat without limitations and low BMI (15.5% and 13.6%, respectively). Altogether the studied variables explained 36% of the variation in walking distance. The data gathered in clinical examination give useful information for the assessment of walking ability in relatively healthy older women. Resting ECG does not give clinically significant additional information for the assessment in subjects without overt cardiac disease.
The objective of this work was to evaluate the post-treatment of an anaerobic recalcitrant effluent (anaerobically-treated weak black liquor, AnE) in an aerobic, upflow reactor packed with "biocubes" of Trametes versicolor immobilized onto small cubes of holm oak wood. The treated effluent (named anaerobic effluent; AnE) from an anaerobic fluidized bed reactor was fed to an up-flow aerobic fungal packed bed reactor (PBR). Two HRT were tested in this unit, namely 5 and 2.5days; the PBR operated 60days at 5-day HRT and 35days at 2.5-day HRT. The aerobic packed bench scale reactor was a glass column 1.5L total geometric volume containing 0.75L biocubes of T. versicolor immobilized onto holm oak wood small cubes of 5mm side. The reactor was operated at 25 degrees C. The pH of the AnE was adjusted to 4.5 before feeding; no carbohydrates or other soluble carbon source was supplemented. The fungal packed bed bioreactor averaged organic matter removals of 30% and 32% COD basis, during an experimental run of 60days at 5-day HRT and 35days at 2.5-day HRT, respectively. Colour and ligninoids contents were removed at higher percentages (69% and 54% respectively, average of both HRT). There was no significant difference between reactor performance at 5- and 2.5-day HRT, so, operation at 2.5-day HRT is recommended since reactor throughput is double. Activity of manganese peroxidase and laccase was found during the entire operation of the fungal PBR whereas lignin peroxidase activity practically disappeared in the second operation period. In general, enzyme activities were higher in the first period of operation (5-day HRT) than at 2.5-day HRT. To the best of our knowledge, this is one of the few works that demonstrated extended performance (3months) of a fungal bioreactor for the treatment of a recalcitrant wastewater with no supplementation of glucose or other expensive, soluble carbohydrate.
Previous studies in young and middle-aged men and women have shown that resting electrocardiographic (ECG) variables are influenced by genetic factors. However, the extent to which resting ECG variables are influenced by genetic factors in older women is unknown. Thus, the aim of this study was to estimate the relative contribution of genetic and environmental influences to individual differences in resting ECG variables among older female twins without overt cardiac diseases.
Two new heliangolides, incomptines C (3) and D (4), were isolated from the leaves of Decachaeta incompta. The structures were established by spectroscopic methods and confirmed by X-ray crystallography. The antiprotozoal activity of incomptines C and D was evaluated. Additionally, the chromatographic profile of the leaves and roots extracts were compared to identify incomptines A-D (1-4) in each extract.
Chemical investigation of the aerial parts of Salvia herbacea led to the isolation of eight new neo-clerodane diterpenes (1-8), named tehuanins A-H, and three known compounds. The structures of these compounds were determined by analysis of their spectroscopic data. Three of the new diterpenes possess a 1,8-epoxy group (1-3). This unusual structural feature was confirmed by X-ray diffraction of 1. The structure of the previously isolated 1?,10?-epoxysalviarin was revised. The absolute configuration of 6 was established by X-ray diffraction analysis of its bromo derivative 6a. Cytotoxic and anti-inflammatory activities of these diterpenes were examined. None of the compounds were considered to be cytotoxic; however, compound 7 exhibited anti-inflammatory activity comparable to that of indomethacin.
Flavones were directly alkylated at the C-3 position in moderate yields using a xanthate-based oxidative radical addition procedure. This methodology is a suitable synthetic tool for the direct substitution of the vinylic and unactivated C-H bond of the C ring of the flavone by an alkyl functionality under neutral conditions.
Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P < 2.31 × 10(-10)) at 31 loci, including 11 for which there have not been previous reports of associations to a metabolic trait or disorder. Analyses of Finnish twin pairs suggested that the metabolic measures reported here show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The identification of such associations may provide substantial insight into cardiometabolic disorders.
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