Urinary cholesterol: its association with a macromolecular protein- lipid complex

The cholesterol-containing complexes in the urine of normal subjects and patients with diseases accompanied by hyperexcretion of urinary cholesterol were characterized. In normal subjects, the major portion of the recovered urinary cholesterol was eluted in the void volume fractions after gel chromatography on Bio-Gel A-5m; this suggested an association with a macromolecular complex above 5 X 10(6) daltons. A comparable elution pattern was seen in most of the urines of the patients with benign or malignant diseases of the kidneys or the urogenital tract. However, in single patients with hyperexcretion of urinary cholesterol, considerable amounts of cholesterol were detected in the included volume of the column. This was caused by additional excretion of high density lipoproteins or both high and low density lipoproteins in the urine which could be identified in these fractions by agarose electrophoresis and immunodiffusion. These results indicate that the macromolecular complex represents the majority of the recovered urinary cholesterol in normal subjects and in disease states with known hyperexcretion. Macroscopically, the isolated cholesterol- containing complex in the void volume fractions was turbid, and electron microscopy showed lipoprotein-like particles with diameters ranging from 300 to 700 A. The chemical analysis revealed median values of protein (46.0%), triglycerides (16.3%), cholesterol (8.2%), and phospholipids (29.5%) in normal subjects and comparable results in the patients with benign or malignant diseases of the kidney and the urogenital tract. Ethanolamine glycerophospholipids, phosphatidylcholine, sphingomyelin, and phosphatidylserine were the main phospholipid components. After ultracentrifugation in a CsCl gradient, the cholesterol-containing complex was found between densities 1.1 and 1.3 g/ml. By SDS polyacrylamide electrophoresis, up to 17 protein subunits in the molecular weight range of 14,000 to 87,500 were separated. Immunodiffusion studies showed in about 40% precipitin lines against anti-human albumin, but no reactions against anti-human apoHDL and anti-human apoLDL. However, immunodiffusion of the macromolecular complex against anti-liver-specific and anti-kidney- specific lipoproteins revealed single precipitin lines. In conclusion, the isolated cholesterol-containing urinary complex showed many characteristics of membrane-associated protein-lipid particles of the human kidney and even the liver. These proteolipids are the major source of urinary cholesterol in normal and disease states

PRODUÇÃO DE BIOGÁS A PARTIR DA CODIGESTÃO DE ÁGUA RESIDUÁRIA DE SUINOCULTURA, VINHAÇA E GLICEROL BRUTO EM REATOR COM ALIMENTAÇÃO SEMICONTÍNUA

O estudo teve como objetivo a avaliação da produção de biogás utilizando como substrato misturas de glicerol bruto, vinhaça e água residual de suinocultura (ARS), visando o estudo dos efeitos destes substratos tanto na eficiência de tratamento dos efluentes, como no volume de gás produzido. Inicialmente, foi determinada a mistura ótima destes substratos utilizando reatores em escala laboratorial em regime batelada. Os melhores resultados tanto para a produção de metano quanto para a remoção da carga orgânica nos efluentes foram obtidos utilizando concentrações de vinhaça e glicerol nas concentrações de 5%. Já a mistura ótima destes substratos foi de 3,22 % para a vinhaça e 4,28 % de glicerol. Na sequência, foi realizada a biodigestão em regime semicontínuo utilizando as proporções obtidas para a mistura ótima, alcançando incrementos na produção de metano da ordem de 300%.ABSTRACTThe study aimed to assess the biogas production using crude glycerol mixtures, vinasse and waste water swine (ARS) as substrate, aimed at study of effects of these substrates in the efficiency of effluent treatment, as the volume of gas produced. It was initially given the optimum mix of these substrates using laboratory-scale reactors in batch operation. The bests results both for the production of methane as the removal of the organic load in effluents were obtained using concentrations of vinasse and glycerol at concentrations of 5%. Already the great mixture of these substrates was 3.22 percent to stillage and 4.28% glycerol. Following, the semi-continuous biodigestion using the proportions obtained for optimum mixing reached increments on methane production in the order of 300%

INFLUÊNCIA DA APLICAÇÃO DE ÁGUA RESÍDUARIA DE SUINOCULTURA NO VOLUME E ÍNDICE DE ACIDEZ DO ÓLEO DE SOJA

Com crescimento populacional acelerado, se surge uma demanda alimentícia crescente para o mundo. Produção essa, por sua vez, de responsabilidade do agronegócio. Consequentemente, os sistemas agropecuários de produção de alimentos originam vários tipos de resíduos orgânicos, apresentando alto poder poluente, especialmente para os recursos hídricos, devido a sua elevada Demanda Química de Oxigênio (DQO). Esses resíduos quando manejados e utilizados adequadamente, revertem-se em fornecedores nutricionais, os quais podem melhorar as condições do solo bem como a produtividade, e consequentemente elevam o volume de matéria-prima para o biodiesel, uma vez que mais de 80% desse biocombustível advém do óleo de soja. A atual pesquisa teve como intuito analisar a influência da utilização de água residuária da suinocultura na cultura da soja, visando aumentar o volume produzido e índice de acidez do óleo extraído a partir de dois solventes distintos, no intuito de avaliar o índice de acidez dos ésteres produzidos. Por fim notou-se o potencial do ciclohexano como solvente alternativo na extração lipídica da soja. Além disso, observou-se que a utilização de ARS como fertilizantes não influenciou significativamente no volume de óleo produzido bem como no índice de acidez da mistura de ésteres produzida

Prevalence-Dependent Costs of Parasite Virulence

Costs of parasitism are commonly measured by comparing the performance of infected groups of individuals to that of uninfected control groups. This measure potentially underestimates the cost of parasitism because it ignores indirect costs, which may result from the modification of the competitiveness of the hosts by the parasite. In this context, we used the host-parasite system consisting of the yellow fever mosquito Aedes aegypti and the microsporidian parasite Vavraia culicis to address this question: Do infected individuals exert a more or less intense intraspecific competition than uninfected individuals? Our experimental results show that, indeed, infected hosts incur a direct cost of parasitism: It takes them longer to become adults than uninfected individuals. They also incur an indirect cost, however, which is actually larger than the direct cost: When grown in competition with uninfected individuals they develop even slower. The consequence of this modification of competitiveness is that, in our system, the cost of parasitism is underestimated by the traditional measure. Moreover, because the indirect cost depends on the frequency of interactions between infected and uninfected individuals, our results suggest that the real cost of parasitism, i.e., virulence, is negatively correlated with the prevalence of the parasite. This link between prevalence and virulence may have dynamical consequences, such as reducing the invasion threshold of the parasite, and evolutionary consequences, such as creating a selection pressure maintaining the host's constitutive resistance to the parasite

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies