Scaling Theory of the Anderson Transition in Random Graphs: Ergodicity and Universality.

We study the Anderson transition on a generic model of random graphs with a tunable branching parameter 1

Two scenarios for quantum multifractality breakdown.

We expose two scenarios for the breakdown of quantum multifractality under the effect of perturbations. In the first scenario, multifractality survives below a certain scale of the quantum fluctuations. In the other one, the fluctuations of the wave functions are changed at every scale and each multifractal dimension smoothly goes to the ergodic value. We use as generic examples a one-dimensional dynamical system and the three-dimensional Anderson model at the metal-insulator transition. Based on our results, we conjecture that the sensitivity of quantum multifractality to perturbation is universal in the sense that it follows one of these two scenarios depending on the perturbation. We also discuss the experimental implications.

New insights on nucleoside 2'-deoxyribosyltransferases: a versatile biocatalyst for one-pot one-step synthesis of nucleoside analogs.

In recent years, glycosiltransferases have arisen as standard biocatalysts for the enzymatic synthesis of a wide variety of natural and non-natural nucleosides. Such enzymatic synthesis of nucleoside analogs catalyzed by nucleoside phosphorylases and 2'-deoxyribosyltransferases (NDTs) has demonstrated to be an efficient alternative to the traditional multistep chemical methods, since chemical glycosylation reactions include several protection-deprotection steps. This minireview exhaustively covers literature reports on this topic with the final aim of presenting NDTs as an efficient option to nucleoside phosphorylases for the synthesis of natural and non-natural nucleosides. Detailed comments about structure and catalytic mechanism of described NDTs, as well as their possible biological role, substrate specificity, and advances in detection of new enzyme specificities towards different non-natural nucleoside synthesis are included. In addition, optimization of enzymatic transglycosylation reactions and their application in the synthesis of natural and non-natural nucleosides have been described. Finally, immobilization of NDTs is shown as a practical procedure which leads to the preparation of very interesting biocatalysts applicable to industrial nucleoside synthesis.

Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.

BACKGROUND: Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. METHODS: Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. RESULTS: All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. CONCLUSIONS: Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson's disease.

Global and regional cortical thinning in first-episode psychosis patients: relationships with clinical and cognitive features.

BACKGROUND: The thickness of the cortical mantle is a sensitive measure for identifying alterations in cortical structure. We aimed to explore whether first episode schizophrenia patients already show a significant cortical thinning and whether cortical thickness anomalies may significantly influence clinical and cognitive features. METHOD: We investigated regional changes in cortical thickness in a large and heterogeneous sample of schizophrenia spectrum patients (n=142) at their first break of the illness and healthy controls (n=83). Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using brains2. The contribution of sociodemographic, cognitive and clinical characterictics was investigated. RESULTS: Patients showed a significant total cortical thinning (F=17.55, d=-0.62, p<0.001) and there was a diffuse pattern of reduced thickness (encompassing frontal, temporal and parietal cortices) (all p's<0.001, d's>0.53). No significant group×gender interactions were observed (all p's>0.15). There were no significant associations between the clinical and pre-morbid variables and cortical thickness measurements (all r's<0.12). A weak significant negative correlation between attention and total (r=-0.24, p=0.021) and parietal cortical thickness (r=-0.27, p=0.009) was found in patients (thicker cortex was associated with lower attention). Our data revealed a similar pattern of cortical thickness changes related to age in patients and controls. CONCLUSIONS: Cortical thinning is independent of gender, age, age of onset and duration of the illness and does not seem to significantly influence clinical and functional symptomatology. These findings support a primary neurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia.

Acylase enzymes disrupting quorum sensing alter the transcriptome and phenotype of Pseudomonas aeruginosa, and the composition of bacterial biofilms from wastewater treatment plants.

Biofilms represent an essential way of life and colonization of new environments for microorganisms. This feature is regulated by quorum sensing (QS), a microbial communication system based on autoinducer molecules, such as N-acyl-homoserine lactones (AHLs) in Gram negative bacteria. In artificial ecosystems, like Wastewater Treatment Plants (WWTPs), biofilm attachment in filtration membranes produces biofouling. In this environment, the microbial communities are mostly composed of Gram-negative phyla. Thus, we used two AHLs-degrading enzymes, obtained from Actinoplanes utahensis (namely AuAAC and AuAHLA) to determine the effects of degradation of QS signals in the biofilm formation, among other virulence factors, of a Pseudomonas aeruginosa strain isolated from a WWTP, assessing molecular mechanisms through transcriptomics. Besides, we studied the possible effects on community composition in biofilms from activated sludge samples. Although the studied enzymes only degraded the AHLs involved in one of the four QS systems of P. aeruginosa, these activities produced the deregulation of the complete QS network. In fact, AuAAC -the enzyme with higher catalytic efficiency- deregulated all the four QS systems. However, both enzymes reduced the biofilm formation and pyocyanin and protease production. The transcriptomic response of P. aeruginosa affected QS related genes, moreover, transcriptomic response to AuAAC affected mainly to QS related genes. Regarding community composition of biofilms, as expected, the abundance of Gram-negative phyla was significantly decreased after enzymatic treatment. These results support the potential use of such AHLs-degrading enzymes as a method to reduce biofilm formation in WWTP membranes and ameliorate bacterial virulence.

Kinetic mechanism of beta-glucosidase from Trichoderma reesei QM 9414.

beta-Glucosidase is a key enzyme in the hydrolysis of cellulose to D-glucose. beta-Glucosidase was purified from cultures of Trichoderma reesei QM 9414 grown on wheat straw as carbon source. The enzyme hydrolyzed cellobiose and aryl beta-glucosides. The double-reciprocal plots of initial velocity vs. substrate concentration showed substrate inhibition with cellobiose and salicin. However, when p-nitrophenyl beta-D-glucopyranoside was the substrate no inhibition was observed. The corresponding kinetic parameters were: K = 1.09 +/- 0.2 mM and V = 2.09 +/- 0.52 mumol.min-1.mg-1 for salicin; K = 1.22 +/- 0.3 mM and V = 1.14 +/- 0.21 mumol.min-1.mg-1 for cellobiose; K = 0.19 +/- 0.02 mM and V = 29.67 +/- 3.25 mumol.min-1.mg-1 for p-nitrophenyl beta-D-glucopyranoside. Studies of inhibition by products and by alternative product supported an Ordered Uni Bi mechanism for the reaction catalyzed by beta-glucosidase on p-nitrophenyl beta-D-glucopyranoside as substrate. Alternative substrates as salicin and cellobiose, a substrate analog such as maltose and a product analog such as fructose were competitive inhibitors in the p-nitrophenyl beta-D-glucopyranoside hydrolysis.

Multifractality of quantum wave functions in the presence of perturbations.

We present a comprehensive study of the destruction of quantum multifractality in the presence of perturbations. We study diverse representative models displaying multifractality, including a pseudointegrable system, the Anderson model, and a random matrix model. We apply several types of natural perturbations which can be relevant for experimental implementations. We construct an analytical theory for certain cases and perform extensive large-scale numerical simulations in other cases. The data are analyzed through refined methods including double scaling analysis. Our results confirm the recent conjecture that multifractality breaks down following two scenarios. In the first one, multifractality is preserved unchanged below a certain characteristic length which decreases with perturbation strength. In the second one, multifractality is affected at all scales and disappears uniformly for a strong-enough perturbation. Our refined analysis shows that subtle variants of these scenarios can be present in certain cases. This study could guide experimental implementations in order to observe quantum multifractality in real systems.

Serum iron in catatonic and noncatatonic psychotic patients.

BACKGROUND: Since low serum iron has been reported in a variety of neuropsychiatric motor disorders, this study was conducted to examine serum iron in patients with a catatonic disorder. METHODS: Forty catatonic and 40 noncatatonic psychotic patients were studied in relation to serum iron levels. The association of serum iron with other clinical variables was also examined. RESULTS: Catatonics had significantly lower mean serum iron than noncatatonics. Ferropenia (serum iron < 50 micrograms/dL) was significantly more prevalent in the catatonic (35%) than in the noncatatonic (7.5%) group. Severity of catatonic symptoms was inversely correlated with level of serum iron, this being due to the negative catatonic symptoms (r = -.34, p = .002). CONCLUSIONS: A subgroup of catatonic patients had ferropenia. Lower serum iron level was associated with both the presence of a categorically defined catatonic syndrome and the severity of the negative catatonic symptoms.

Identification of an essential glutamate residue in the active site of endoglucanase III from Trichoderma reesei.

n-Propyl, n-butyl and n-pentyl beta-cellobiosides with a reactive omega-epoxide in their aglycon completely and irreversibly inactivate endoglucanase III from Trichoderma reesei. The pentyl derivative was found to be most effective. From these affinity labeling experiments evidence was found for the implication of Glu329 in the reaction mechanism. This is discussed in relation to other structural/functional data known for endoglucanase III and several other family A glycanases.

Stereochemistry of phenyl alpha-nitronyl nitroxide radicals

An extensive investigation of the conformations adopted by the family of phenyl alpha-nitronyl nitroxides has been carried out. A database containing 110 crystal structures was used in a statistical study of the solid-state geometries and conformations of these radicals. This study revealed that the favoured conformations involve a twisted distortion in the imidazolyl rings and a twist between the aromatic and heterocyclic rings in the molecules. As a consequence, these radicals show two types of preferred conformations in the solid state: the pseudo-anti enantiomeric pair and the pseudo-eclipsed pair, the latter type being the most statistically probable. A new chiral member of this group of radicals that bears a lactate moiety, (R)-1, and its corresponding racemic compound, (R,S)-1, have been prepared in order to study the influence of chiral induction from the stereogenic centre on the torsion angle between the aromatic and heterocyclic rings of the alpha-nitronyl nitroxides. The X-ray crystal structures of the enantiopure and racemic compounds, which both reveal chains of molecules sustained by strong O-H...O hydrogen bonds between the carboxylic acid group and the ON group of the radical in the solid, as well as their magnetic properties have been determined. Remarkably, the molecules with a given stereogenic centre have a single helical sense between their component rings, even in the racemic crystal. Chiral induction from the stereogenic centre to the radical unit has also been proved by CD spectroscopy in the solid state. The results of these experiments have been rationalised by ab initio calculations of the spectra.

Clinical applications of pharmacogenetics in psychiatry.

Pharmacogenetic research has identified response-related mutant variants in metabolic enzymes and drug-targeted receptors. Allelic variants of dopaminergic and serotonergic receptors have been associated with clinical outcome and adverse events such as movement disorders. Deficient metabolic enzymes have been related to drug accumulation and toxic events. This information will help to design safer and more efficient drugs. However, the field is moving rapidly towards a new goal: the application of pharmacogenetics as a clinical tool for the prediction of treatment outcome. The first studies in this direction have proved the feasibility of using genetic information for the prediction of response to antipsychotic drugs and to treatment of Alzheimer's disease. New strategies investigating genes related to specific symptoms and side-effects have produced encouraging results that can contribute to the improvement of the levels and accuracy of the predictions. This review tries to summarise recent advances and provides an overview of future clinical applications.

Chemical modification of beta-glucosidase from Trichoderma reesei QM 9414.

The inhibition of beta-glucosidase from Trichoderma reesei QM 9414 by several specific reagents was studied. Diethylpyrocarbonate (DEP) nearly abolished the enzyme activity at concentrations above 10 mM. The presence of substrate or analogs protected the enzyme against inactivation. The reaction followed pseudo-first order kinetics with a second-order rate constant of 0.02 mM-1.min-1. The pH-dependence of the inactivation showed the involvement of a group with a pK of 5.2. Difference spectra at 242 nm and the reversal of the inactivation in the presence of 1 M hydroxylamine indicated the modification of histidine residues. Statistical analysis of residual fractional activity versus the number of modified histidine residues indicated that one histidine residue is essential for catalysis. p-Hydroxymercuribenzoate completely inhibited the enzyme at concentrations of the reagent above 2 mM. Substrate or analogs protected the enzyme against inactivation. The reaction followed pseudo-first order kinetics with a second-order rate constant of 0.002 mM-1.min-1. Treatment of the modified enzyme with 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) showed that one cysteine residue was essential for activity. At pH 5.0 2-ethoxy-1-ethoxy-carbonyl-1,2-dihydroquinoline (EEDQ) inactivated the enzyme according to pseudo-first order kinetics with a second-order rate constant of 0.12 min-1. The pH-dependence of the inactivation showed the involvement of a group with a pK of 5.64, indicating the modification of a carboxyl group essential for activity.

Chemical modification of histidyl residues in D-amino acid oxidase from Rhodotorula gracilis.

D-Amino acid oxidase was inactivated by DEP at 30 degrees C and pH 7.5. The reaction followed pseudo-first-order kinetics with a second-order rate constant of 0.254 mM-1.min-1. The pH dependence of the inactivation showed the involvement of a group with a pK of 6.6. The presence of substrate or benzoate protected the enzyme against inactivation. Difference spectra at 242 nm and the reversal of the inactivation in the presence of 1 M hydroxylamine or 0.1 M NaOH pointed to the modification of histidine residues. The statistical analysis of the residual fractional activity versus the number of modified histidine residues led to the conclusion that one histidine residue is essential for the enzyme activity.

Childhood schizotypy and positive symptoms in schizophrenic patients predict schizotypy in relatives.

BACKGROUND: Schizotypy is one phenotypic expression of the familial-genetic liability to schizophrenia, but its precise relationship to frank psychotic symptoms remains unclear. We, therefore, set out to examine the relationships between (a) premorbid personality in schizophrenic patients, (b) the psychopathology they showed, and (c) schizotypal traits in their relatives. METHOD: Ninety consecutively admitted schizophrenic patients were interviewed with the Present State Examination (PSE). Their mothers were interviewed concerning their childhood personality and social adjustment, and 121 of their well relatives were evaluated with three different schizotypal scales. Factor analyses were carried out on (a) the nine main psychotic symptoms from the patients' PSE interview, and on (b) the schizotypal features derived from the scales completed by the first-degree relatives. Correlation coefficients were calculated between premorbid personality traits, and factor scores in probands and in relatives. RESULTS: No relationship was found between childhood schizoid-schizotypal personality traits and any particular dimension of psychopathology in patients. The positive syndrome in patients was correlated with higher scores for relatives on the three schizotypy scales, but did not predict any specific pattern of schizotypy in the relatives. Premorbid schizoid-schizotypal traits were also correlated with schizotypy in the relatives. CONCLUSIONS: Schizotypy in relatives has a familial relationship with schizoid-schizotypal traits in the childhood, and with positive symptoms during the illness, of schizophrenic patients.

Activation and stabilization of penicillin V acylase from streptomyces lavendulae in the presence of glycerol and glycols.

Penicillin V acylase (EC 3.5.1.11) from Streptomyces lavendulae showed both enhanced activity and stability in mixed water/glycerol and water/glycols solvents. The catalytic activity was increased up to a critical concentration of these cosolvents, but further addition of the latter led to a gradual protein deactivation. The highest stabilizing effect was achieved in the presence of glycerol. Thermal stability was increased proportionally to the concentration of glycerol and glycols in the reaction mixture only if the amount added is below the threshold concentration. Reaction conditions that allow simultaneously enhanced activity and stability in the hydrolysis of penicillin V catalyzed by penicillin V acylase from S. lavendulae could be established.

Uracilato and 5-halouracilato complexes of Cu(II), Zn(II) and Ni(II). X-ray structures of [Cu(uracilato-N(1))(2)(NH(3))(2)].2(H(2)O), [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2), [Ni(5-chlorouracilato-N(1))(2)(en)(2)].2H(2)O and [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O).

Four new complexes of uracilato and 5-halouracilato with the divalent metal ions Cu(II), Zn(II) and Ni(II) were obtained and structurally characterized. [Cu(uracilato- N(1))(2)(NH(3))(2)].2(H(2)O) (1) and [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2) (2) complexes present distorted square planar co-ordination geometry around the metal ion. Although an additional axial water molecule is present [Cu(II)-OH(2)=2.89 A (for 1) and 2.52 A (for 2)] in both cases, only in the complex 2 would be considered in the limit of a bond distance. The Zn(II) in [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O) presents a tetrahedral co-ordination with three ammonia molecules and the N(1) of the corresponding uracilato moiety. A non-coordinated uracilato molecule is present as a counterion and a recognition between co-ordinated and free ligands, by means a tandem of H-bonds, should be mentioned. Finally, the complex [Ni(5-chlorouracilato-N(1))(2)(en)(2)] (H(2)O)(2) (where en is ethylenediamine) presents a typical octahedral trans co-ordination with additional hydrogen bonds between 5-chlorouracilato and the NH(2) groups of ethylenediamine units.

[Ehlers-Danlos's syndrome type II. A family study]. / Síndrome de Ehlers-Danlos tipo II. Estudio familiar.

We describe the presence of EDS type II in a family whose diagnosis was lately established by medical consultation of one of its members suffering from hyperuricemia and gout. We stress the relevance of an early diagnosis of this syndrome as a means to prevent and reduce as much as possible cardiovascular, hemorrhagic and surgical systemic complications associated to this disease.

[Lupus myopathy refractory to steroid treatment]. / Miopatía lúpica refractaria al tratamiento esteroideo.

A 58-year-old patient with lupus erythematosus (LE) who needed treatment with azathioprine, due to resistant myopathy to steroids, is presented. Clinical and histological features, as well as therapy, are discussed.