Optimization of biotechnological systems through geometric programming.

Background: In the past, tasks of model based yield optimization in metabolic engineering were either approached with stoichiometric models or with structured nonlinear models such as S-systems or linear-logarithmic representations. These models stand out among most others, because they allow the optimization task to be converted into a linear program, for which efficient solution methods are widely available. For pathway models not in one of these formats, an Indirect Optimization Method (IOM) was developed where the original model is sequentially represented as an S-system model, optimized in this format with linear programming methods, reinterpreted in the initial model form, and further optimized as necessary.

The role of dietary protein on lipotoxicity.

The worldwide increase in degenerative diseases is in part due to modifications in the lifestyle including the diet. Epidemiological, clinical, and experimental evidence shows that soy protein may prevent lipotoxicity in non-adipose tissues during obesity. The molecular mechanism by which soy protein prevents lipotoxicity involves a reduction in the insulin/glucagon ratio, resulting in a down-regulation of lipogenic genes mediated by the transcription factor sterol regulatory element-binding protein (SREBP)-1, and up-regulation of SREBP-2 to reduce serum cholesterol.

Detection of potential enzyme targets by metabolic modelling and optimization: application to a simple enzymopathy.

Motivation: A very promising approach in drug discovery involves the integration of available biomedical data through mathematical modelling and data mining. We have developed a method called optimization program for drug discovery (OPDD) that allows new enzyme targets to be identified in enzymopathies through the integration of metabolic models and biomedical data in a mathematical optimization program. The method involves four steps: (i) collection of the necessary information about the metabolic system and disease; (ii) translation of the information into mathematical terms; (iii) computation of the optimization programs prioritizing the solutions that propose the inhibition of a reduced number of enzymes and (iv) application of additional biomedical criteria to select and classify the solutions.

Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP-treated monkeys.

We have examined dopaminergic cell survival after alteration of the subthalamic nucleus (STN) in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The STN was lesioned with kainic acid (B series) or underwent deep brain stimulation (DBS) at high frequency (C series). In another series, MPTP-treated and non-MPTP-treated monkeys had no STN alteration (intact animals; A series).

Interindividual glucocorticoid sensitivity in young healthy subjects: the role of glucocorticoid receptor alpha and beta isoforms ratio.

Only few studies have addressed the interindividual variation and tissue specificity of glucocorticoid (GC) sensitivity in healthy individuals, a phenomenon observed in pathological conditions. Alternative splicing of the glucocorticoid receptor (GR) produces alpha and beta isoforms. GRbeta has dominant-negative effects on hormone-induced GRalpha effects, and an increased expression of the GRbeta has been associated with glucocorticoid resistance.

Pancreatic insulin secretion in rats fed a soy protein high fat diet depends on the interaction between the amino acid pattern and isoflavones.

Obesity is frequently associated with the consumption of high carbohydrate/fat diets leading to hyperinsulinemia. We have demonstrated that soy protein (SP) reduces hyperinsulinemia, but it is unclear by which mechanism. Thus, the purpose of the present work was to establish whether SP stimulates insulin secretion to a lower extent and/or reduces insulin resistance, and to understand its molecular mechanism of action in pancreatic islets of rats with diet-induced obesity.

Percutaneous endocardial and epicardial ablation of hypotensive ventricular tachycardia with percutaneous left ventricular assist in the electrophysiology laboratory.

Ventricular tachycardia (VT) in the setting of structural heart disease is challenging to treat with percutaneous catheter ablation due to the presence of complex substrate, multiple morphologies, hemodynamic instability, and epicardial circuits. When substrate-based approaches fail, however, it may be impossible to map and ablate hemodynamically unstable arrhythmias. We describe a novel approach to endocardial and epicardial mapping and ablation of hypotensive VT using a percutaneous left ventricular assist device in the electrophysiology laboratory, permitting near-surgical access to cardiac structures.

Phylogenetic autocorrelation and evolutionary interpretation of the higher-taxon approach for biodiversity analyses.

Although in most recent broad-scale analyses, diversity is measured by counting the number of species in a given area or spatial unity (species richness), a 'top-down' approach has been used sometimes, counting higher-taxon (genera, family) instead of species with some advantages. However, this higher-taxon approach is quite empirical and the cut-off level is usually arbitrarily defined. In this work, we show that the higher-taxon approach could be theoretically linked with models of phenotypic diversification by means of phylogenetic autocorrelation analysis in such a way that the taxonomic (or phylogenetic) rank to be used could not be necessarily arbitrary.

Evaluation of the flora of northern Mexico for in vitro antimicrobial and antituberculosis activity.

The aim of the present study was to evaluate the potential antimicrobial activity of 14 plants used in northeast México for the treatment of respiratory diseases, against drug-sensitive and drug-resistant strains of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae type b and Mycobacterium tuberculosis. Forty-eight organic and aqueous extracts were tested against these bacterial strains using a broth microdilution test. No aqueous extracts showed antimicrobial activity, whereas most of the organic extracts presented antimicrobial activity against at least one of the drug-resistant microorganisms tested.

Characterization and regulation of the gene expression of amino acid transport system A (SNAT2) in rat mammary gland.

Amino acid transport via system A plays an important role during lactation, promoting the uptake of small neutral amino acids, mainly alanine and glutamine. However, the regulation of gene expression of system A [sodium-coupled neutral amino acid transporter (SNAT)2] in mammary gland has not been studied. The aim of the present work was to understand the possible mechanisms of regulation of SNAT2 in the rat mammary gland.

[Massive acute hydrothorax secondary to peritoneal dialysis in a hemolytic uremic syndrome. Report of a case].

Massive acute hydrothorax (MAH) is a severe and unusual noninfectious complication of peritoneal dialysis (PD). It can lead to acute respiratory failure and may diminish the effectiveness of the dialytic therapy. Many therapeutic strategies for this complication are employed, ranging from conservative methods like reduction of the volume of the dialysate and the transitory interruption of the PD, to more aggressive therapies as the closure of diaphragmatic defects by videothoracoscopy with or without pleurodesis.

Regulation of lipid metabolism by soy protein and its implication in diseases mediated by lipid disorders.

Soybeans have a high-quality protein that has been consumed for approximately 5000 years in Oriental countries. The awareness that soy products are healthy has increased their consumption in Western countries. Substantial data from epidemiological surveys and nutritional interventions in humans and animals indicate that soy protein reduces serum total and low-density lipoprotein (LDL) cholesterol and triglycerides as well as hepatic cholesterol and triglycerides.

[Metabolism of cholesterol and fatty acids in nephrotic syndrome and its regulation by sterol regulatory element binding proteins (SREBP's). Effect of soy protein consumption].

Hyperlipidemia occurs during nephrotic syndrome (NS). It is known that cholesterol and fatty acid biosynthesis is controlled by the transcription factors sterol regulatory element binding proteins (SREBPs). Soy protein consumption reduces the concentration of these lipids, although its mechanism of action is not well known.

Synthesis of long-chain polyunsaturated fatty acids in lactating mammary gland: role of Delta5 and Delta6 desaturases, SREBP-1, PPARalpha, and PGC-1.

The purpose of this work was to study whether rat lactating mammary gland can synthesize PUFAs through the expression of Delta5 and Delta6 desaturases (Delta5D and Delta6D), whether these enzymes are regulated by the transcription factors sterol-regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator-activated receptor alpha (PPARalpha) and the coactivator peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), and whether these desaturases are regulated by the lipid concentration in the diet. The results showed that on day 12 of lactation, approximately 35% of the linoleic acid in the diet, which is the precursor of PUFAs, is transferred to the mammary gland. There was expression of Delta5D and Delta6D in mammary gland, and it was regulated by the corn oil content in the diet.

Mitochondrial branched chain aminotransferase gene expression in AS-30D hepatoma rat cells and during liver regeneration after partial hepatectomy in rat.

Branched chain aminotransferase (BCAT) is the first enzyme in the catabolism of branched chain amino acids (BCAA). Unlike other amino acid degrading enzymes present in liver, BCAT is only expressed in extrahepatic tissues, and is not regulated by dietary protein, glucagon or glucocorticoids. However, the mitochondrial (m) isoform of BCAT is highly expressed in the fetal liver and rapidly decays after birth.

[Molecular mechanisms of action and health benefits of polyunsaturated fatty acids].

Essential polyunsaturated fatty acids (PUFAs), linoleic acid n6 (LA) and linolenic acid (ALA) n3 obtained from the diet are precursors of the long-chain polyunsaturated fatty acids (Lc-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) respectively. Consumption of PUFAs is related with a better neurological and cognitive development in newborns. It has been demonstrated that consumption of n-6 and n-3 PUFAs decreases blood triglycerides by increasing fatty acid oxidation through activation of PPARalpha or by reducing the activation of SREBP-1 inhibiting lipogenesis.

Biochemical characterization and membrane fluidity of membranous vesicles isolated from boar seminal plasma.

Mammalian seminal plasma contains membranous vesicles (MV), which differ in composition and origin. Among these particles, human prostasomes and equine prostasome-like MV have been the most studied. The aim of the present work is to characterize the biochemical composition and membrane fluidity of MV isolated from boar seminal plasma.

Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats.

Hepatic steatosis is commonly present during the development of insulin resistance, and it is a clear sign of lipotoxicity attributable in part to an accelerated lipogenesis. There is evidence that a soy protein diet prevents the overexpression of hepatic sterol-regulatory element binding protein-1 (SREBP-1), decreasing lipid accumulation. Therefore, the aim of the present work was to study whether a soy protein diet may prevent the development of fatty liver through the regulation of transcription factors involved in lipid metabolism in hyperinsulinemic and hyperleptinemic Zucker obese fa/fa rats.

Design of metabolic engineering strategies for maximizing L-(-)-carnitine production by Escherichia coli. Integration of the metabolic and bioreactor levels.

In this work metabolic engineering strategies for maximizing L-(-)-carnitine production by Escherichia coli based on the Biochemical System Theory and the Indirect Optimization Method are presented. The model integrates the metabolic and the bioreactor levels using power-law formalism. Based on the S-system model, the Indirect Optimization Method was applied, leading to profiles of parameter values that are compatible with both the physiology of the cells and the bioreactor system operating conditions.

[Multicentric study of Brazilian patients with 21-hydroxylase deficiency: a genotype-phenotype correlation].

We analyzed the clinical and molecular data of 205 patients with the three different clinical forms of 21-hydroxylase deficiency, in whom the clinical and molecular diagnosis were already defined. The most frequent mutations were I2 splice in the salt wasting form, I172N in the simple virilizing and V281L in the nonclassical form, presenting similar frequencies as those observed in other populations. We found a lower frequency of 21-hydroxylase gene deletion, similar to that previously identified in Argentinean and Mexican populations.

Regulation by glucagon of the rat histidase gene promoter in cultured rat hepatocytes and human hepatoblastoma cells.

Histidase (Hal), the amino acid-degrading enzyme of histidine, is regulated by the protein content of the diet and by hormones such as glucocorticoids and glucagon. However, glucagon can activate the following two possible transduction pathways: protein kinase A (PKA) and protein kinase C (PKC). The aim of this study was to isolate the 5'-flanking region of rat Hal gene to locate possible cAMP- and glucocorticoid-responsive elements and to identify whether the activation of the Hal promoter by glucagon occurs via PKA or PKC.

[Peroxisome proliferator-activated receptors (PPARs) in obesity and insulin resistance development].

The peroxisome proliferator-activated receptors (PPARs) are a family of nuclear transcription factors that belong to the steroid receptor superfamily. PPARs family includes PPARalpha, PPARbeta/delta, PPARgamma1 and PPARgamma2. PPARs form an heterodimer with the 9-cis retinoic acid receptor (RXR) and bind to response elements present in target genes activated by these transcription factors.

Dynamics of sulfur amino acids in mammalian brain: assessment of the astrocytic-neuronal cysteine interaction by a mathematical hybrid model.

A mathematically hybrid model was used to analyze three mechanisms by which cysteine could be produced in the brain to be used as preferential substrate in the synthesis of neuronal glutathione. In that way, the fluxes of sulfur-compounds at the brain-blood barrier were integrated with their transport in astrocytes and neurons, and with their metabolism in astrocytes. We concluded that cysteine, in contrast with its precursor cystine, would not be taken up from the blood at the blood-brain barrier, but instead it must be lost continuously from astrocytes.

Renal protection by a soy diet in obese Zucker rats is associated with restoration of nitric oxide generation.

The obese Zucker rat is a valuable model for studying kidney disease associated with obesity and diabetes. Previous studies have shown that substitution of animal protein with soy ameliorates the progression of renal disease. To explore the participation of nitric oxide (NO) and caveolin-1 in this protective effect, we evaluated proteinuria, creatinine clearance, renal structural lesions, nitrites and nitrates urinary excretion (UNO(2)(-)/NO(3)V), and mRNA and protein levels of neuronal NO synthase (nNOS), endothelial NOS (eNOS), and caveolin-1 in lean and fatty Zucker rats fed with 20% casein or soy protein diet.

Comparison of activity monitors to estimate energy cost of treadmill exercise.

Purpose: To evaluate the validity of five physical activity monitors available for research: the CSA, the TriTrac-R3D, the RT3, the SenseWear Armband, and the BioTrainer-Pro.

Methods: A total of 10 healthy men and 11 healthy women performed 10 min of treadmill walking at 54, 80, and 107 mxmin and treadmill running at 134, 161, 188, and 214 mxmin. The CSA, TriTrac-R3D, RT3, and BioTrainer-Pro accelerometers were placed side by side bilaterally at the waist in the axillary position, and the SenseWear Armband monitors were placed bilaterally on the posterior portion of each arm in the mid-humeral position.