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S-Adenosylmethionine (SAM) synthetase of yeast and hyphal-phase cells of the dimorphic fungusCandida albicans was characterized by kinetic analysis and response to inhibitors. The enzyme from yeast-phase cells has a Km of 0.17 mM for methionine, 0.14 mM for ATP, and is inhibited (in vitro) by dimethyl-sulfoxide, methionine sulfone, and methionine sulfoxide. The hyphal-phase SAM synthetase has a Km of 0.06 mM for methionine, 0.02 mM for ATP, and its activity (in vitro) is enhanced by the substances that inhibit the yeast-phase enzyme. These data strongly suggest that isozymes of SAM synthetase are present inC. albicans and that they are possibly morphology specific. In vivo studies revealed that synthesis of the enzyme is repressed by the addition of methionine to the growth medium and that specific activity of the enzyme increases when intracellular SAM levels are lowered. In addition, it was shown that the increase in specific activity seen during yeast → hypha morphogenesis and in yeast cells grown in a methionine-free medium involves de novo protein synthesis.

OBJECTIVE: The aim of this study was to investigate the possible role of the caspase 7 (CASP7) in susceptibility to rheumatoid arthritis (RA). METHODS: Genotyping of three single nucleotide polymorphisms (SNPs) of the CASP7 gene: rs11593766 (G/ T), rs2227310 (C/G) and rs2227309 (G/A) was performed in a total of 906 RA patients and 528 matched healthy controls using TaqMan assays. All the subjects were of Spanish Caucasian origin. A relative quantification of mRNA encoding the non-functional variant of procaspase 7 (isoform beta) vs functional isoforms was performed in total RNA from 32 healthy individuals using real-time PCR. RESULTS: Only the rs2227309 SNP was found to be associated with susceptibility to RA. Frequency of the G allele was significantly higher among RA patients [overall frequency of the G allele 74.0% in cases vs 68.4% in controls, P = 0.001, Odds ratio (OR) = 1.32, 95% Confidence intervals (95% CI) 1.11-1.56] and a higher frequency of GG homozygous individuals was found in the RA patient group (overall frequency of GG genotype 56.0% in cases and 46.4% in controls, P = 0.0005, OR = 1.47, 95%CI 1.18-1.83). A statistically significant deviation was observed to compare the relative expression of the procaspase 7 isoform beta in samples from individuals stratified according their rs2227309 genotypes (AA + AG: 1.36 +/- 0.55, n = 19, vs GG: 2.35 +/- 0.74, n = 13; P = 0.0002). CONCLUSION: Our results support involvement of the CASP7 gene in the susceptibility to RA. The higher production of the no functional variant of CASP7 by individuals with a particular genotype could be the basis of this association.

We will generalize the projective model structure in the category of unbounded complexes of modules over a commutative ring to the category of unbounded complexes of quasi-coherent sheaves over the projective line. Concretely we will define a locally projective model structure in the category of complexes of quasi-coherent sheaves on the projective line. In this model structure the cofibrant objects are the dg-locally projective complexes. We also describe the fibrations of this model structure and show that the model structure is monoidal. We point out that this model structure is necessarily different from other known model structures such as the injective model structure and the locally free model structure.

Devido ao custo da energia, tem crescido o interesse pelo uso de cerâmicas refratárias porosas como isolantes térmicos para aplicações em altas temperaturas. Isso se deve ao fato desses materiais aliarem propriedades intrínsecas das cerâmicas, como inércia química e refratariedade, à baixa condutividade térmica dos porosos. Uma das técnicas utilizadas na obtenção desses materiais consiste na adição de compostos orgânicos à matriz cerâmica, os quais volatilizam durante a queima. Essa técnica pode ter seu desempenho aprimorado (porosidade controlada) pela utilização da heterocoagulação entre as partes inorgânicas e orgânicas. O objetivo desse trabalho foi avaliar o impacto da heterocoagulação na fabricação de cerâmicas porosas utilizando PVC ou amido como aditivo orgânico e alumina como componente inorgânico. Foram definidas as condições mais favoráveis à heterocoagulação para os dois incorporadores. Independente do tipo de incorporador, o aumento do teor utilizado resultou em cerâmicas mais porosas. Entretanto, um teor máximo de 50vol% do material orgânico foi escolhido, uma vez que maiores teores resultam em uma resistência mecânica insatisfatória. Verificou-se ainda que, em comparação com o processo convencional, as cerâmicas produzidas por heterocoagulação apresentaram maior homogeneidade microestrutural e resistência mecânica. The crisis faced by the energy sector has led to a growing interest in the use of refractory porous ceramics as high temperature insulators, due to their unique combination of properties: chemical inertia, refractoriness and low thermal conductivity. Among the several techniques employed in the production of these materials, the addition of organic particles, which volatilize during the first heat-up, to the ceramic matrix is one of the most promising techniques. This procedure can be optimized in order to attain a better control over the porosity using the heterocoagulation of the inorganic and organic parts of a suspension. The purpose of the present work was to evaluate the impact of the heterocoagulation on the production of porous ceramics using PVC and starch as organic and alumina as inorganic compounds. The most suitable conditions to promote heterocoagulation of the constituents were previously determined. The increasing of the volume fraction of the organic parts generated more porous materials for both additives. However, the maximum amount of organics was set in 50 vol.% in order to achieve acceptable mechanical strength. It was also found out that compared to the conventional process, the porous ceramics obtained by heterocoagulation presented superior microestrutural homogeneity and mechanical strength.

Recent studies suggest an association between Chlamydia pneumoniae infection with atherosclerosis, including cerebrovascular disease. We investigated the prevalence of Chlamydial seropositivity in patients with acute ischaemic stroke syndrome compared with age- and sex-matched control subjects. Specific antibodies (IgA) to C. pneumoniae were measured by microimmunofluorescence in both the clinical group (n=91) and the control group (n=112). Forty patients (43.9%) and 34 controls (30.3%) had positive IgA titres (P < 0.05). The pooled data from this and previous series yielded 45% of seropositivity in cerebrovascular patients vs. 19% in control subjects (P < 0.001). In conclusion, we suggest an association between chronic infection by C. pneumoniae and acute ischaemic stroke.

Macrophages are able to produce, export, and transfer fatty acids to lymphocytes in culture. The purpose of this study was to examine if labelled fatty acids could be transferred from macrophages to pancreatic islets in co-culture. We found that after 3 h of co-culture the transfer of fatty acids to pancreatic islets was: arachidonic >> oleic > linoleic = palmitic. Substantial amounts of the transferred fatty acids were found in the phospholipid fraction; 87.6% for arachidonic, 59.9% for oleic, 53.1% for palmitic, and 36.9% for linoleic acids. The remaining radioactivity was distributed among the other lipid fractions analysed (namely polar lipids, cholesterol, fatty acids, triacylglycerol and cholesterol ester), varying with the fatty acid used. For linoleic acid, a significant proportion (63.1%) was almost equally distributed in these lipid fractions. Also, it was observed that transfer of fatty acids from macrophages to pancreatic islets is time-dependent up to 24 h, being constant and linear with time for palmitic acid and remaining constant after 12 h for oleic acid. These results lead us to postulate that in addition to the serum, circulating monocytes may also be a source of fatty acids to pancreatic islets, mainly arachidonic acid.

Cytotoxic T-lymphocyte antigen 4 (CTLA4) polymorphisms located in the promotor region at positions -318 (C/T) and in exon 1 (49 A/ G) were investigated in 138 Spanish patients (37 men and 101 women) with rheumatoid arthritis and in 305 ethnically-matched healthy controls. When the allelic and genotypic frequencies corresponding to the CTLA4 -318 position were compared, no significant differences between patients and controls were found. However, when the CTLA4 49 A/G polymorphism was analysed, a significant increase of A/G heterozygous individuals among female patients (48.5% vs. 33.8% in controls; P=0.008; OR=2.0) was observed. This increase was absent among males (37.8%, P=NS). Analysis of the CTLA4 49 polymorphism with respect to HLA-DRB1 typing demonstrated a significant increase of A/G heterozygosity in the HLA-DR3-positive patient group compared with HLA-DR3-negative patient group (14/19, 74% vs. 49/119, 41%; P=0.009, OR=4.0). The increase of A/G genotype among HLA-DR3-positive patients was found in both males (4/6, 67%) and females' (10/13, 77%), although statistical differences were only reached in the female group. These results provide new insight into this complex association, confirm previous data from other studies, and suggest that the CTLA4 gene could be involved in the pathogenesis of rheumatoid arthritis.

Increasing evidence suggests the presence of local modulators that contribute to testicular function regulation in rats. The seminiferous tubules and Sertoli cell factors influence the steroidogenic activity of Leydig cells. Addition of Sertoli cell conditioned media to primary cultures of adult rat Leydig cells produces in a dose-dependent manner an inhibition of testosterone production with a concomitant decrease in the C21 delta 4-intermediates of the steroidogenic pathway, modifying the C21/C19 ratios in normal cells. The nature and mechanisms of action of this putative modulating activity are currently under study.

Two tripeptide amides with stuctures similar to thyrotropin releasing hormone were isolated from human seminal fluid and their amino acid sequences determined. The peptides were purified by gel exclusion from Sephadex G50 and were detected by radioimmunoassay with thyrotropin releasing hormone antibody; in addition, N-terminally extended forms were demonstrated by radioimmunoassay after trypsin digestion. Further purification of the tripeptides was by chromatography on SP-Sephadex C25 and by high performance liquid chromatography on C18 Microbondapak using an HCl/acetonitrile gradient. After exclusion from mini-columns of SP-Sephadex C25 and DEAE-Sephadex A25, two neutral peptides were obtained in homogeneous form by high performance liquid chromatography with an HCl/methanol gradient. Amino acid analysis gave the following compositions: Glu, 0.74, Phe, 1.0, Pro, 1.0; and Glu, 1.72, Pro, 1.0. Both peptides possessed a blocked N terminus, but after opening the pyroglutamyl ring the sequences Glu-Phe-Pro and Glu-Glx-Pro were demonstrated. The chromatographic properties of the endogenous peptides were identical to the properties of the corresponding synthetic peptides. The structure of pGlu-Phe-Pro (where p-indicates pyro-) amide was confirmed by fast atom bombardment mass spectrometry. The presence in human semen of three structurally related peptides, pGlu-Phe-Pro amide, pGlu-Gln-Pro amide, and the previously reported pGlu-Glu-Pro amide (Cockle, S. M., Aitken, A., Beg, F., and Smyth, D. G. (1989) J. Biol. Chem. 264, 7788-7791), suggests that this series of peptides may have evolved to fulfil complementary biological roles.

The yeast Candida albicans is considered a dangerous opportunist in a compromised host. Both phases of growth are thought to be pathogenic, however, evidence suggests that the hyphal phase is the more virulent. It has been proposed that the increased virulence lies in the ability of hyphae to digest and penetrate host tissue, thus enabling access of fungal cells to the deeper tissues. However, this one characteristic does not sufficiently explain the organism's success as a pathogen. Recently, high-frequency, colonial morphology switching systems were described in C. albicans. We obtained some of these variants and tested them for the ability to produce extracellular phospholipase(s), a generally accepted mechanism of pathogenesis in many microorganisms. Using egg yolk agar plates, we showed that all variants produced the enzyme. However, one produced significantly more than the others.

By radioimmunoassay (RIA) we studied tumor-associated trypsin inhibitor (TATI) in 152 serum samples, divided into three groups: 35 healthy subjects, used as controls; 25 individuals with benign pathology of the ear, nose and throat (ENT) region; 92 serial samples obtained from 69 patients with malignant disease of the head and neck. The malignant ENT group were classified in four stages according to the degree of tumor activity. The TATI concentrations (mean +/- SD) were as follows: control group, 16.0 +/- 3.4; benign group, 17.1 +/- 6.7; A0, 14.8 +/- 11.5; A1, 12.1 +/- 3.5; A2, 17.01 +/- 1.4; A3, 43.0 +/- 54.9.

Posttraumatic formation of either aortico-ventricular or coronary arterio-ventricular fistulas are rare, albeit well-documented events. A case is presented involving crush injury to the chest complicated by an acute inferior wall myocardial infarction and later associated with an aortico-right ventricular fistula. Progressive right ventricular dilatation dictated subsequent surgical repair in this case, although similar fistulas without dilatation may safely be observed.

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is recognized as the most common hereditary defect of fatty acid oxidation in humans. Death is the outcome of the first attack in about 25% of cases. A point mutation (A to G [corrected] at position 985) of the MCAD gene represents more than 90% of alleles causing MCAD deficiency. The frequency of this allelic variant exhibits considerable geographical variations. In Spain, where the few diagnosed patients are mostly of Gypsy origin, the frequency is low as occurs in other Southern European countries (1 heterozygote among 200 individuals). Here we have analyzed the frequency of the G985 allele among Spanish gypsies. Heterozygotes were detected at a frequency of 1/17, with a 95% confidence interval ranging from 1/11 to 1/39. This represents the highest G985 rate described so far and calls for preventive measures, such as selective screening in this population.

Regarding the article by Provost et al. (Fractured Porous Media under Influence: The Roselend Experiment, Eos, 23 March 2004; pp. 113, 119), I have some comments concerning the interpretation of radon data and the instrumentation used for this purpose. In the first instance, it is obvious that the site presents a great number of advantages for studying the fluid transport phenomena in porous media, and I encourage the authors to continue in this investigation. My first observation is concerning the radon data shown in the article.The authors show the data obtained in one station, using a Barasol® probe to measure radon in the air. The Barasol® probe was created initially to measure radon concentrations in the soil, and its precision is not the same as a probe like an AlphaGUARD®, for example. Moreover, the authors are aware of this limitation. It will be interesting to compare this data with that obtained with the AlphaGUARD®, or in the instrumented chamber described in the article that is 55 m from the tunnel entrance, named the Inner Room by the authors.

The H-atom coordinates were omitted from Tables 2 and 3 on p. 897 [Salvadó, Pertierra, García-Granda, García, Rodríguez & Fernández-Díaz, Acta Cryst. (1996), B52, 896–898]. The values are now listed.

The intracellular level of S-adenosylmethionine increased as the yeast-phase cells of Mucor racemosus were induced to convert to hyphae. This increase correlated well with time course of the conversion in cell type and was independent of the metabolic changes caused by the shift to aerobic conditions. There was no significant change in the intracellular level of spermidine, a polyamine synthesized from putrescine and the propylamine group of S-adenosylmethionine. Spermine was not detected. An examination of protein methylation revealed an increase in the methylation of total protein during the shift in cell type and possible qualitative as well as quantitative changes in specific base proteins.

In the island of Lanzarote of the Province of Las Palmas, which is part of the Spanish archipelago of the Canary Islands, the prevalence of multiple sclerosis is 15 per 100,000. The prevalence of MS in Lanzarote seems related more to ethnic conditions than to geography.

1. The delay time between onset of ESRD and first cadaver kidney transplant varies considerably across patient subgroups. It is shortest for Whites and Asian Americans and longest for Blacks. Patients with blood type O and those highly sensitized have longer delays. 2. The effect of delay time on graft survival, while real and statistically significant, is quantitatively small. 3. Based on an analysis of a large national United States sample, CAPD therapy, compared to other forms of dialysis, does not have an adverse effect on 2-year graft survival.

A case or retroperitoneal perforation of a duodenal ulcer is presented. Firstly was erroneously diagnosed as an acute appendicitis, and operated upon. The result were good but four successives surgical gests became necessary : first, to treat a very severe parietal infection ; after that, to resolve one very impressive gastro-intestinal hemorrhage and lastly, to treat the duodeno-cutaenous fistula and the duodenal ulcer. The published cases in the recent literature are very scanty but similar to ourselves. The difficulties of promp diagnosis, the erroneously planned first operation in seriously ill patients would be the main causes of the very high mortality.

Rheoelectric analogy using apparent mass to obtain static and dynamic stability derivatives for lifting-body reentry vehicles

The extragalactic VHE gamma-ray sky is rich in blazars. These are jetted active galactic nuclei viewed at a small angle to the line-of-sight. Only a handful of objects viewed at a larger angle are known so far to emit above 100 GeV. Multi-wavelength studies of such objects up to the highest energies provide new insights into the particle and radiation processes of active galactic nuclei. We report the results from the first multi-wavelength campaign observing the TeV detected nucleus of the active galaxy IC 310, whose jet is observed at a moderate viewing angle of 10 deg - 20 deg. The multi-instrument campaign was conducted between 2012 Nov. and 2013 Jan., and involved observations with MAGIC, Fermi, INTEGRAL, Swift, OVRO, MOJAVE and EVN. These observations were complemented with archival data from the AllWISE and 2MASS catalogs. A one-zone synchrotron self-Compton model was applied to describe the broad-band spectral energy distribution. IC 310 showed an extraordinary TeV flare at the beginning of the campaign, followed by a low, but still detectable TeV flux. Compared to previous measurements, the spectral shape was found to be steeper during the low emission state. Simultaneous observations in the soft X-ray band showed an enhanced energy flux state and a harder-when-brighter spectral shape behaviour. No strong correlated flux variability was found in other frequency regimes. The broad-band spectral energy distribution obtained from these observations supports the hypothesis of a double-hump structure. The harder-when-brighter trend in the X-ray and VHE emission is consistent with the behaviour expected from a synchrotron self-Compton scenario. The contemporaneous broad-band spectral energy distribution is well described with a one-zone synchrotron self-Compton model using parameters that are comparable to those found for other gamma-ray-emitting misaligned blazars., 15 pages, 10 figures. Accepted for publication in A&A